Syringe with PECVD lubricity layer

ABSTRACT

Methods for processing a vessel, for example to provide a gas barrier or lubricity, are disclosed. First and second PECVD or other vessel processing stations or devices and a vessel holder comprising a vessel port are provided. An opening of the vessel can be seated on the vessel port. The interior surface of the seated vessel can be processed via the vessel port by the first and second processing stations or devices. Vessel barrier and lubricity coatings and coated vessels, for example syringes and medical sample collection tubes are disclosed. A vessel processing system is also disclosed.

This is a continuation of U.S. Ser. No. 15/409,165, filed Jan. 18, 2017,now pending, which is a continuation of U.S. Ser. No. 14/305,202, filedJun. 16, 2014, now U.S. Pat. No. 9,572,526, which is a divisional ofU.S. Ser. No. 13/941,154, filed Jul. 12, 2013, now U.S. Pat. No.8,834,954, which is a continuation of U.S. Ser. No. 13/169,811, filedJun. 27, 2011, now U.S. Pat. No. 8,512,796, which is a divisional ofU.S. Ser. No. 12/779,007, filed May 12, 2010, now U.S. Pat. No.7,985,188, which claims the priority of U.S. Provisional Ser. Nos.61/177,984 filed May 13, 2009; 61/222,727, filed Jul. 2, 2009;61/213,904, filed Jul. 24, 2009; 61/234,505, filed Aug. 17, 2009;61/261,321, filed Nov. 14, 2009; 61/263,289, filed Nov. 20, 2009;61/285,813, filed Dec. 11, 2009; 61/298,159, filed Jan. 25, 2010;61/299,888, filed Jan. 29, 2010; 61/318,197, filed Mar. 26, 2010, and61/333,625, filed May 11, 2010. These applications are incorporated hereby reference in their entirety.

Also incorporated by reference in their entirety are the followingEuropean patent applications, all filed May 12, 2010: EP10162755.2;EP10162760.2; EP10162756.0; EP10162758.6; EP10162761.0; andEP10162757.8.

The present invention also relates to the technical field of coatedvessels and fabrication of coated vessels for storing biologicallyactive compounds or blood. For example, the invention relates to avessel processing system for coating of a vessel, to a portable vesselholder for a vessel processing system, to a plasma enhanced chemicalvapor deposition apparatus for coating an interior surface of a vessel,to a method for coating an interior surface of a vessel, to a method forcoating a vessel, and to a method of processing a vessel.

The present disclosure also relates to improved methods for processingvessels, for example multiple identical vessels used for venipunctureand other medical sample collection, pharmaceutical preparation storageand delivery, and other purposes. Such vessels are used in large numbersfor these purposes, and must be relatively economical to manufacture andyet highly reliable in storage and use.

BACKGROUND OF THE INVENTION

Prefilled syringes are commonly prepared and sold so the syringe doesnot need to be filled before use. The syringe can be prefilled withsaline solution, a dye for injection, or a pharmaceutically activepreparation, for some examples.

Commonly, the prefilled syringe is capped at the distal end, as with acap, and is closed at the proximal end by its drawn plunger. Theprefilled syringe can be wrapped in a sterile package before use. To usethe prefilled syringe, the packaging and cap are removed, optionally ahypodermic needle or another delivery conduit is attached to the distalend of the barrel, the delivery conduit or syringe is moved to a useposition (such as by inserting the hypodermic needle into a patient'sblood vessel or into apparatus to be rinsed with the contents of thesyringe), and the plunger is advanced in the barrel to inject thecontents of the barrel.

One important consideration in manufacturing pre-filled syringes is thatthe contents of the syringe desirably will have a substantial shelflife, during which it is important to isolate the material filling thesyringe from the barrel wall containing it, to avoid leaching materialfrom the barrel into the prefilled contents or vice versa.

Since many of these vessels are inexpensive and used in largequantities, for certain applications it will be useful to reliablyobtain the necessary shelf life without increasing the manufacturingcost to a prohibitive level. It is also desirable for certainapplications to move away from glass vessels, which can break and areexpensive to manufacture, in favor of plastic vessels which are rarelybroken in normal use (and if broken do not form sharp shards fromremnants of the vessel, like a glass tube would). Glass vessels havebeen favored because glass is more gas tight and inert to pre-filledcontents than untreated plastics. Also, due to its traditional use,glass is well accepted, as it is known to be relatively innocuous whencontacted with medical samples or pharmaceutical preparations and thelike.

A further consideration when regarding syringes is to ensure that theplunger can move at a constant speed and with a constant force when itis pressed into the barrel. For this purpose, a lubricity layer, eitheron one or on both of the barrel and the plunger, is desirable.

SUMMARY OF THE INVENTION

An aspect of the invention is a syringe comprising a barrel defining alumen and having an interior surface slidably receiving a plunger. Thesyringe barrel may be made of thermoplastic base material. A lubricitylayer, characterized as defined in the Definition Section, is appliedto, e.g., the barrel interior surface, the plunger, or both by PECVD.The lubricity layer may be made from an organosilicon precursor, and maybe less than 1000 nm thick. A surface treatment is carried out on thelubricity layer in an amount effective to reduce leaching of thelubricity layer, the thermoplastic base material, or both into thelumen, i.e. effective to form a solute retainer on the surface. Thelubricity layer and solute retainer are composed, and present inrelative amounts, effective to provide a breakout force, plunger slidingforce, or both that is less than the corresponding force required in theabsence of the lubricity layer and solute retainer.

Another aspect of the invention is a method of plasma-enhanced chemicalvapor deposition (PECVD) treatment of a first vessel, including severalsteps. A first vessel is provided having an open end, a closed end, andan interior surface. At least a first gripper is configured forselectively holding and releasing the closed end of the first vessel.The closed end of the first vessel is gripped with the first gripperand, using the first gripper, transported to the vicinity of a vesselholder configured for seating to the open end of the first vessel. Thefirst gripper is then used to axially advance the first vessel and seatits open end on the vessel holder, establishing sealed communicationbetween the vessel holder and the interior of the first vessel.

At least one gaseous reactant is introduced within the first vesselthrough the vessel holder. Plasma is formed within the first vesselunder conditions effective to form a reaction product of the reactant onthe interior surface of the first vessel.

The first vessel is then unseated from the vessel holder and, using thefirst gripper or another gripper, the first vessel is axiallytransported away from the vessel holder. The first vessel is thenreleased from the gripper used to axially transport it away from thevessel holder.

Yet another aspect of the invention is a vessel having a wall at leastpartially enclosing a lumen. The wall has an interior polymer layerenclosed by an exterior polymer layer. One of the polymer layers is alayer at least 0.1 mm thick of a cyclic olefin copolymer (COC) resindefining a water vapor barrier. Another of the polymer layers is a layerat least 0.1 mm thick of a polyester resin.

The wall includes an oxygen barrier layer of SiO_(x), in which x in thisformula is from about 1.5 to about 2.9, alternatively from about 1.5 toabout 2.6, alternatively about 2, having a thickness of from about 10 toabout 500 angstroms.

Other aspects of the invention will be apparent from the followingspecification and claims.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic diagram showing a vessel processing systemaccording to an embodiment of the disclosure.

FIG. 2 is a schematic sectional view of a vessel holder in a coatingstation according to an embodiment of the disclosure.

FIG. 3 is a section taken along section lines A-A of FIG. 2.

FIG. 4 is a diagrammatic view of the operation of a vessel transportsystem to place and hold a vessel in a process station.

FIG. 5 is an exploded longitudinal sectional view of a syringe and capadapted for use as a prefilled syringe.

FIG. 6 is a view generally similar to FIG. 2 showing a capped syringebarrel and vessel holder in a coating station according to an embodimentof the disclosure.

FIG. 7 is a perspective view of a blood collection tube assembly, havinga closure, according to still another embodiment of the invention.

FIG. 8 is a fragmentary section of the blood collection tube and closureassembly of FIG. 7.

FIG. 9 is an isolated section of an elastomeric insert of the closure ofFIGS. 7 and 8.

FIG. 10 is a perspective view of a double-walled blood collection tubeassembly according to still another embodiment of the invention.

FIG. 11 is a schematic sectional view of an array of gas delivery tubesand a mechanism for inserting and removing the gas delivery tubes from avessel holder, showing a gas delivery tube in its fully advancedposition.

FIG. 12 is a view similar to FIG. 11, showing a gas delivery tube in anintermediate position.

FIG. 13 is a view similar to FIG. 12, showing a gas delivery tube in aretracted position. The array of gas delivery tubes of FIGS. 11-13 areusable, for example, with the embodiments of FIGS. 1-4, 6, and 14-16.The mechanism of FIGS. 11-13 is usable, for example, with the gasdelivery tube embodiments of FIGS. 2, 3, 4, 6, 14, and 15.

FIG. 14 is a view showing a mechanism for delivering vessels to betreated and a cleaning reactor to a PECVD coating apparatus. Themechanism of FIG. 14 is usable with the vessel inspection apparatus ofFIGS. 1 and 4, for example.

FIG. 15 is a schematic view of an assembly for treating vessels. Theassembly is usable with the apparatus of FIGS. 1-6 and 11-14.

FIG. 16 is a diagrammatic view of the embodiment of FIG. 15.

The following reference characters are used in the drawing figures:

20 Vessel processing system 22 Injection molding machine 24 Visualinspection station 26 Inspection station (pre-coating) 28 Coatingstation 30 Inspection station (post-coating) 32 Optical sourcetransmission station (thickness) 34 Optical source transmission station(defects) 36 Output 38 Vessel holder 40 Vessel holder 42 Vessel holder44 Vessel holder 46 Vessel holder 48 Vessel holder 50 Vessel holder 52Vessel holder 54 Vessel holder 56 Vessel holder 58 Vessel holder 60Vessel holder 62 Vessel holder 64 Vessel holder 66 Vessel holder 68Vessel holder 70 Conveyor 72 Transfer mechanism (on) 74 Transfermechanism (off) 80 Vessel 82 Opening 84 Closed end 86 Wall 88 Interiorsurface 90 Barrier layer 92 Vessel port 94 Vacuum duct 96 Vacuum port 98Vacuum source 100 O-ring (of 92) 102 O-ring (of 96) 104 Gas inlet port106 O-ring (of 100) 108 Probe (counter electrode) 110 Gas delivery port(of 108) 112 Vessel holder 114 Housing (of 50 or 112) 116 Collar 118Exterior surface (of 80) 120 Vessel holder (array) 122 Vessel port 130Frame 132 Light source 134 Side channel 136 Shut-off valve 138 Probeport 140 Vacuum port 142 PECVD gas inlet port 144 PECVD gas source 146Vacuum line (to 98) 148 Shut-off valve 150 Flexible line (of 134) 152Pressure gauge 154 Interior of vessel 80 160 Electrode 162 Power supply164 Sidewall (of 160) 166 Sidewall (of 160) 168 Closed end (of 160) 202Tube transport 204 Suction cup 250 Syringe barrel 252 Syringe 254Interior surface (of 250) 256 Back end (of 250) 258 Plunger (of 252) 260Front end (of 250) 262 Cap 264 Interior surface (of 262) 268 Vessel 270Closure 272 Interior facing surface 274 Lumen 276 Wall-contactingsurface 278 Inner surface (of 280) 280 Vessel wall 282 Stopper 284Shield 286 Lubricity layer 288 Barrier layer 408 Inner wall (FIG. 11)410 Outer wall (FIG. 11) 510 Inner electrode 512 Inner electrode 514Insertion and removal mechanism 516 Flexible hose 518 Flexible hose 520Flexible hose 522 Valve 524 Valve 526 Valve 528 Electrode cleaningstation 530 Inner electrode drive 532 Cleaning reactor 534 Vent valve536 Second gripper 538 Conveyer 539 Solute retainer 540 Open end (of532) 574 Main vacuum valve 576 Vacuum line 578 Manual bypass valve 580Bypass line 582 Vent valve 584 Main reactant gas valve 586 Main reactantfeed line 588 Organosilicon liquid reservoir 590 Organosilicon feed line(capillary) 592 Organosilicon shut-off valve 594 Oxygen tank 596 Oxygenfeed line 598 Mass flow controller 600 Oxygen shut-off valve 614Headspace 616 Pressure source 618 Pressure line 620 Capillary connection

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention will now be described more fully with reference tothe accompanying drawings, in which several embodiments are shown. Thisinvention can, however, be embodied in many different forms and shouldnot be construed as limited to the embodiments set forth here. Rather,these embodiments are examples of the invention, which has the fullscope indicated by the language of the claims. Like numbers refer tolike or corresponding elements throughout.

Definition Section

In the context of the present invention, the following definitions andabbreviations are used:

RF is radio frequency; sccm is standard cubic centimeters per minute.

The term “at least” in the context of the present invention means “equalor more” than the integer following the term. The word “comprising” doesnot exclude other elements or steps, and the indefinite article “a” or“an” does not exclude a plurality unless indicated otherwise.

“First” and “second” or similar references to, e.g., processing stationsor processing devices refer to the minimum number of processing stationsor devices that are present, but do not necessarily represent the orderor total number of processing stations and devices. These terms do notlimit the number of processing stations or the particular processingcarried out at the respective stations.

For purposes of the present invention, an “organosilicon precursor” is acompound having at least one of the linkage:

which is a tetravalent silicon atom connected to an oxygen atom and anorganic carbon atom (an organic carbon atom being a carbon atom bondedto at least one hydrogen atom). A volatile organosilicon precursor,defined as such a precursor that can be supplied as a vapor in a PECVDapparatus, is an optional organosilicon precursor. Optionally, theorganosilicon precursor is selected from the group consisting of alinear siloxane, a monocyclic siloxane, a polycyclic siloxane, apolysilsesquioxane, an alkyl trimethoxysilane, a linear silazane, amonocyclic silazane, a polycyclic silazane, a polysilsesquiazane, and acombination of any two or more of these precursors.

In the context of the present invention, “essentially no oxygen” or(synonymously) “substantially no oxygen” is added to the gaseousreactant in some embodiments. This means that some residual atmosphericoxygen can be present in the reaction space, and residual oxygen fed ina previous step and not fully exhausted can be present in the reactionspace, which are defined here as essentially no oxygen present.Essentially no oxygen is present in the gaseous reactant if the gaseousreactant comprises less than 1 vol % O₂, for example less than 0.5 vol %O₂, and optionally is O₂-free. If no oxygen is added to the gaseousreactant, or if no oxygen at all is present during PECVD, this is alsowithin the scope of “essentially no oxygen.”

A “vessel” in the context of the present invention can be any type ofvessel with at least one opening and a wall defining an interiorsurface. The term “at least” in the context of the present inventionmeans “equal or more” than the integer following the term. Thus, avessel in the context of the present invention has one or more openings.One or two openings, like the openings of a sample tube (one opening) ora syringe barrel (two openings) are preferred. If the vessel has twoopenings, they can be of same or different size. If there is more thanone opening, one opening can be used for the gas inlet for a PECVDcoating method according to the present invention, while the otheropenings are either capped or open. A vessel according to the presentinvention can be a sample tube, e.g. for collecting or storingbiological fluids like blood or urine, a syringe (or a part thereof, forexample a syringe barrel) for storing or delivering a biologicallyactive compound or composition, e.g. a medicament or pharmaceuticalcomposition, a vial for storing biological materials or biologicallyactive compounds or compositions, a pipe, e.g. a catheter fortransporting biological materials or biologically active compounds orcompositions, or a cuvette for holding fluids, e.g. for holdingbiological materials or biologically active compounds or compositions.

A vessel can be of any shape, a vessel having a substantiallycylindrical wall adjacent to at least one of its open ends beingpreferred. Generally, the interior wall of the vessel is cylindricallyshaped, like, e.g. in a sample tube or a syringe barrel. Sample tubesand syringes or their parts (for example syringe barrels) arecontemplated.

A “lubricity layer” according to the present invention is a coatingwhich has a lower frictional resistance than the uncoated surface. Inother words, it reduces the frictional resistance of the coated surfacein comparison to a reference surface which is uncoated. The presentlubricity layers are primarily defined by their lower frictionalresistance than the uncoated surface and the process conditionsproviding lower frictional resistance than the uncoated surface, andoptionally can have a composition according to the empirical compositionSi_(w)O_(x)C_(y)H_(z), as defined in this Definition Section.“Frictional resistance” can be static frictional resistance and/orkinetic frictional resistance. One of the optional embodiments of thepresent invention is a syringe part, e.g. a syringe barrel or plunger,coated with a lubricity layer. In this contemplated embodiment, therelevant static frictional resistance in the context of the presentinvention is the breakout force as defined herein, and the relevantkinetic frictional resistance in the context of the present invention isthe plunger sliding force as defined herein. For example, the plungersliding force as defined and determined herein is suitable to determinethe presence or absence and the lubricity characteristics of a lubricitylayer in the context of the present invention whenever the coating isapplied to any syringe or syringe part, for example to the inner wall ofa syringe barrel. The breakout force is of particular relevance forevaluation of the coating effect on a prefilled syringe, i.e. a syringewhich is filled after coating and can be stored for some time, e.g.several months or even years, before the plunger is moved again (has tobe “broken out”).

The “plunger sliding force” in the context of the present invention isthe force required to maintain movement of a plunger in a syringebarrel, e.g. during aspiration or dispense. It can advantageously bedetermined using the ISO 7886-1:1993 test described herein and known inthe art. A synonym for “plunger sliding force” often used in the art is“plunger force” or “pushing force”.

The “breakout force” in the context of the present invention is theinitial force required to move the plunger in a syringe, for example ina prefilled syringe.

Both “plunger sliding force” and “breakout force” and methods for theirmeasurement are described in more detail in subsequent parts of thisdescription.

“Slidably” means that the plunger is permitted to slide in a syringebarrel.

In the context of this invention, “substantially rigid” means that theassembled components (ports, duct, and housing, explained further below)can be moved as a unit by handling the housing, without significantdisplacement of any of the assembled components respecting the others.Specifically, none of the components are connected by hoses or the likethat allow substantial relative movement among the parts in normal use.The provision of a substantially rigid relation of these parts allowsthe location of the vessel seated on the vessel holder to be nearly aswell known and precise as the locations of these parts secured to thehousing.

In the following, the apparatus for performing the present inventionwill be described first, followed by the coating methods, coatings andcoated vessels, and the uses according to the present invention.

Vessel Processing System Having Multiple Processing Stations andMultiple Vessel Holders

A vessel processing system is contemplated comprising a first processingstation, a second processing station, a multiplicity of vessel holders,and a conveyor. The first processing station is configured forprocessing a vessel having an opening and a wall defining an interiorsurface. The second processing station is spaced from the firstprocessing station and configured for processing a vessel having anopening and a wall defining an interior surface.

At least some, optionally all, of the vessel holders include a vesselport configured to receive and seat the opening of a vessel forprocessing the interior surface of a seated vessel via the vessel portat the first processing station. The conveyor is configured fortransporting a series of the vessel holders and seated vessels from thefirst processing station to the second processing station for processingthe interior surface of a seated vessel via the vessel port at thesecond processing station.

Referring first to FIG. 1, a vessel processing system generallyindicated as 20 is shown. The vessel processing system can includeprocessing stations which more broadly are contemplated to be processingdevices. The vessel processing system 20 of the illustrated embodimentcan include an injection molding machine 22 (which can be regarded as aprocessing station or device), additional processing stations or devices24, 26, 28, 30, 32, and 34, and an output 36 (which can be regarded as aprocessing station or device). At a minimum, the system 20 has at leasta first processing station, for example station 28, and a secondprocessing station, for example 30, 32, or 34.

Any of the processing stations 22-36 in the illustrated embodiment canbe a first processing station, any other processing station can be asecond processing station, and so forth.

The embodiment illustrated in FIG. 1 can include eight processingstations or devices: 22, 24, 26, 28, 30, 32, 34, and 36. The exemplaryvessel processing system 20 includes an injection molding machine 22, apost-molding inspection station 24, a pre-coating inspection station 26,a coating station 28, a post-coating inspection station 30, an opticalsource transmission station 32 to determine the thickness of thecoating, an optical source transmission station 34 to examine thecoating for defects, and an output station 36.

The system 20 can include a transfer mechanism 72 for moving vesselsfrom the injection molding machine 22 to a vessel holder 38. Thetransfer mechanism 72 can be configured, for example, as a robotic armthat locates, moves to, grips, transfers, orients, seats, and releasesthe vessels 80 to remove them from the vessel forming machine 22 andinstall them on the vessel holders such as 38.

The system 20 also can include a transfer mechanism at a processingstation 74 for removing the vessel from one or more vessel holders suchas 66, following processing the interior surface of the seated vesselsuch as 80 (FIG. 1). The vessels 80 are thus movable from the vesselholder 66 to packaging, storage, or another appropriate area or processstep, generally indicated as 36. The transfer mechanism 74 can beconfigured, for example, as a robotic arm that locates, moves to, grips,transfers, orients, places, and releases the vessels 80 to remove themfrom the vessel holders such as 38 and place them on other equipment atthe station 36.

The processing stations or devices 32, 34, and 36 shown in FIG. 1optionally carry out one or more appropriate steps downstream of thecoating and inspection system 20, after the individual vessels 80 areremoved from the vessel holders such as 64. Some non-limiting examplesof functions of the stations or devices 32, 34, and 36 include:

-   -   placing the treated and inspected vessels 80 on a conveyor to        further processing apparatus;    -   adding chemicals to the vessels;    -   capping the vessels;    -   placing the vessels in suitable processing racks;    -   packaging the vessels; and    -   sterilizing the packaged vessels.

The vessel processing system 20 as illustrated in FIG. 1 also caninclude a multiplicity of vessel holders (or “pucks,” as they can insome embodiments resemble a hockey puck) respectively 38 through 68, anda conveyor generally indicated as an endless band 70 for transportingone or more of the vessel holders 38-68, and thus vessels such as 80, toor from the processing stations 22, 24, 26, 28, 30, 32, 34, and 36.

The processing station or device 22 can be a device for forming thevessels 80. One contemplated device 22 can be an injection moldingmachine. Another contemplated device 22 can be a blow molding machine.Vacuum molding machines, draw molding machines, cutting or millingmachines, glass drawing machines for glass or other draw-formablematerials, or other types of vessel forming machines are alsocontemplated. Optionally, the vessel forming station 22 can be omitted,as vessels can be obtained already formed.

Vessel Holders

The portable vessel holders 38-68 are provided for holding and conveyinga vessel having an opening while the vessel is processed. The vesselholder includes a vessel port, a second port, a duct, and a conveyablehousing.

The vessel port is configured to seat a vessel opening in a mutuallycommunicating relation. The second port is configured to receive anoutside gas supply or vent. The duct is configured for passing one ormore gases between a vessel opening seated on the vessel port and thesecond port. The vessel port, second port, and duct are attached insubstantially rigid relation to the conveyable housing. Optionally, theportable vessel holder weighs less than five pounds. An advantage of alightweight vessel holder is that it can more readily be transportedfrom one processing station to another.

In certain embodiments of the vessel holder the duct more specificallyis a vacuum duct and the second port more specifically is a vacuum port.The vacuum duct is configured for withdrawing a gas via the vessel portfrom a vessel seated on the vessel port. The vacuum port is configuredfor communicating between the vacuum duct and an outside source ofvacuum. The vessel port, vacuum duct, and vacuum port can be attached insubstantially rigid relation to the conveyable housing.

The vessel holders are shown, for example, in FIG. 2. The vessel holder50 has a vessel port 82 configured to receive and seat the opening of avessel 80. The interior surface of a seated vessel 80 can be processedvia the vessel port 82. The vessel holder 50 can include a duct, forexample a vacuum duct 94, for withdrawing a gas from a vessel 80 seatedon the vessel port 92. The vessel holder can include a second port, forexample a vacuum port 96 communicating between the vacuum duct 94 and anoutside source of vacuum, such as the vacuum pump 98. The vessel port 92and vacuum port 96 can have sealing elements, for example O-ring buttseals, respectively 100 and 102, or side seals between an inner or outercylindrical wall of the vessel port 82 and an inner or outer cylindricalwall of the vessel 80 to receive and form a seal with the vessel 80 oroutside source of vacuum 98 while allowing communication through theport. Gaskets or other sealing arrangements can also be used.

The vessel holder such as 50 can be made of any material, for examplethermoplastic material and/or electrically nonconductive material. Or,the vessel holder such as 50 can be made partially, or even primarily,of electrically conductive material and faced with electricallynonconductive material, for example in the passages defined by thevessel port 92, vacuum duct 94, and vacuum port 96. Examples of suitablematerials for the vessel holder 50 are: a polyacetal, for exampleDelrin® polyacetal material sold by E.I. du Pont De Nemours and Company,Wilmington Del.; polytetrafluoroethylene (PTFE), for example Teflon®PTFE sold by E.I. du Pont De Nemours and Company, Wilmington Del.;Ultra-High-Molecular-Weight Polyethylene (UHMWPE); High densityPolyethylene (HDPE); or other materials known in the art or newlydiscovered.

FIG. 2 also illustrates that the vessel holder, for example 50, can havea collar 116 for centering the vessel 80 when it is approaching orseated on the port 92.

Array of Vessel Holders

Yet another approach to treat, inspect, and/or move parts through aproduction system can be to use an array of vessel holders. The arraycan be comprised of individual pucks or be a solid array into which thedevices are loaded. An array can allow more than one device, optionallymany devices, to be tested, conveyed or treated/coated simultaneously.The array can be one-dimensional, for example grouped together to form alinear rack, or two-dimensional, similar to a tub or tray.

Transporting Vessel Holders to Processing Stations

FIGS. 1 and 2 show a method for processing a vessel 80. The method canbe carried out as follows.

A vessel 80 can be provided having an opening 82 and a wall 86 definingan interior surface 88. As one embodiment, the vessel 80 can be formedin and then removed from a mold such as 22. Optionally within 60seconds, or within 30 seconds, or within 25 seconds, or within 20seconds, or within 15 seconds, or within 10 seconds, or within 5seconds, or within 3 seconds, or within 1 second after removing thevessel from the mold, or as soon as the vessel 80 can be moved withoutdistorting it during processing (assuming that it is made at an elevatedtemperature, from which it progressively cools), the vessel opening 82can be seated on the vessel port 92. Quickly moving the vessel 80 fromthe mold 22 to the vessel port 92 reduces the dust or other impuritiesthat can reach the surface 88 and occlude or prevent adhesion of thebarrier or other type of coating 90. Also, the sooner a vacuum is drawnon the vessel 80 after it is made, the less chance any particulateimpurities have of adhering to the interior surface 88.

The interior surface 88 of the seated vessel 80 can be then processedvia the vessel port 92 at the first processing station, which can be, asone example, the barrier application or other type of coating station 28shown in FIG. 2. The vessel holder 50 and seated vessel 80 aretransported from the first processing station 28 to the secondprocessing station, for example the processing station 32. The interiorsurface 88 of the seated vessel 80 can be processed via the vessel port92 at the second processing station such as 32.

Any of the above methods can include the further step of removing thevessel 80 from the vessel holder such as 66 following processing theinterior surface 88 of the seated vessel 80 at the second processingstation or device.

Any of the above methods can include the further step, after theremoving step, of providing a second vessel 80 having an opening 82 anda wall 86 defining an interior surface 88. The opening 82 of the secondvessel such as 80 can be seated on the vessel port 92 of another vesselholder such as 38. The interior surface of the seated second vessel 80can be processed via the vessel port 92 at the first processing stationor device such as 24. The vessel holder such as 38 and seated secondvessel 80 can be transported from the first processing station or device24 to the second processing station or device such as 26. The seatedsecond vessel 80 can be processed via the vessel port 92 by the secondprocessing station or device 26.

Transporting Processing Devices to Vessel Holders or Vice Versa.

Or, the processing stations can more broadly be processing devices, andeither the vessel holders can be conveyed relative to the processingdevices, the processing devices can be conveyed relative to the vesselholders, or some of each arrangement can be provided in a given system.In still another arrangement, the vessel holders can be conveyed to oneor more stations, and more than one processing device can be deployed ator near at least one of the stations. Thus, there is not necessarily aone-to-one correspondence between the processing devices and processingstations.

Using Gripper for Transporting Tube to and from Coating Station

Yet another embodiment is a method of PECVD treatment of a first vessel,including several steps. A first vessel is provided having an open end,a closed end, and an interior surface. At least a first gripper isconfigured for selectively holding and releasing the closed end of thefirst vessel. The closed end of the first vessel is gripped with thefirst gripper and, using the first gripper, transported to the vicinityof a vessel holder configured for seating to the open end of the firstvessel. The first gripper is then used to axially advance the firstvessel and seat its open end on the vessel holder, establishing sealedcommunication between the vessel holder and the interior of the firstvessel.

At least one gaseous reactant is introduced within the first vesselthrough the vessel holder. Plasma is formed within the first vesselunder conditions effective to form a reaction product of the reactant onthe interior surface of the first vessel.

The first vessel is then unseated from the vessel holder and, using thefirst gripper or another gripper, the first vessel is axiallytransported away from the vessel holder. The first vessel is thenreleased from the gripper used to axially transport it away from thevessel holder.

Referring again to FIGS. 4 and 14, a series conveyor 538 can be used tosupport and transport multiple grippers such as 204 through theapparatus and process as described here. The grippers 204 areoperatively connected to the series conveyor 538 and configured forsuccessively transporting a series of at least two vessels 80 to thevicinity of the vessel holder 48 and carrying out the other steps of thecleaning method as described here.

PECVD Apparatus Including Vessel Holder, Internal Electrode, Vessel asReaction Chamber

Another embodiment is a PECVD apparatus including a vessel holder, aninner electrode, an outer electrode, and a power supply. A vessel seatedon the vessel holder defines a plasma reaction chamber, which optionallycan be a vacuum chamber. Optionally, a source of vacuum, a reactant gassource, a gas feed or a combination of two or more of these can besupplied. Optionally, a gas drain, not necessarily including a source ofvacuum, is provided to transfer gas to or from the interior of a vesselseated on the port to define a closed chamber.

The PECVD apparatus can be used for atmospheric-pressure PECVD, in whichcase the plasma reaction chamber does not need to function as a vacuumchamber.

In the embodiment illustrated in FIG. 2, the vessel holder 50 comprisesa gas inlet port 104 for conveying a gas into a vessel seated on thevessel port. The gas inlet port 104 has a sliding seal provided by atleast one O-ring 106, or two O-rings in series, or three O-rings inseries, which can seat against a cylindrical probe 108 when the probe108 is inserted through the gas inlet port 104. The probe 108 can be agas inlet conduit that extends to a gas delivery port at its distal end110. The distal end 110 of the illustrated embodiment can be inserteddeep into the vessel 80 for providing one or more PECVD reactants andother process gases.

Optionally in the embodiment illustrated in FIG. 2, or more generally inany embodiment disclosed, such as the embodiments of FIG. 1, 4, 6, or11-16, a plasma screen can be provided to confine the plasma formedwithin the vessel 80 generally to the volume above the plasma screen.The plasma screen is a conductive, porous material, several examples ofwhich are steel wool, porous sintered metal or ceramic material coatedwith conductive material, or a foraminous plate or disk made of metal(for example brass) or other conductive material. An example is a pairof metal disks having central holes sized to pass the gas inlet 108 andhaving 0.02-inch (0.5 mm) diameter holes spaced 0.04 inches (1 mm)apart, center-to-center, the holes providing 22% open area as aproportion of the surface area of the disk.

The plasma screen 610, for example for embodiments in which the probe108 also functions as an counter electrode, can make intimate electricalcontact with the gas inlet 108 at or near the opening 82 of the tube,syringe barrel, or other vessel 80 being processed. Alternatively, theplasma screen 610 can be grounded, optionally having a common potentialwith the gas inlet 108. The plasma screen 610 reduces or eliminates theplasma in the vessel holder 50 and its internal passages andconnections, for example the vacuum duct 94, the gas inlet port 104, thevicinity of the O-ring 106, the vacuum port 96, the O-ring 102, andother apparatus adjacent to the gas inlet 108. At the same time, theporosity of the plasma screen allows process gases, air, and the like toflow out of the vessel 80 into the vacuum port 96 and downstreamapparatus.

FIG. 15 shows additional optional details of the coating station 28 thatare usable, for example, with the embodiments of FIG. 1-4 or 6. Thecoating station 28 can also have a main vacuum valve 574 in its vacuumline 576 leading to the pressure sensor 152. A manual bypass valve 578is provided in the bypass line 580. A vent valve 582 controls flow atthe vent 404.

Flow out of the PECVD gas source 144 is controlled by a main reactantgas valve 584 regulating flow through the main reactant feed line 586.One component of the gas source 144 is the organosilicon liquidreservoir 588. The contents of the reservoir 588 are drawn through theorganosilicon capillary line 590, which is provided at a suitable lengthto provide the desired flow rate. Flow of organosilicon vapor iscontrolled by the organosilicon shut-off valve 592. Pressure is appliedto the headspace 614 of the liquid reservoir 588, for example a pressurein the range of 0-15 psi (0 to 78 cm. Hg), from a pressure source 616such as pressurized air connected to the headspace 614 by a pressureline 618 to establish repeatable organosilicon liquid delivery that isnot dependent on atmospheric pressure (and the fluctuations therein).The reservoir 588 is sealed and the capillary connection 620 is at thebottom of the reservoir 588 to ensure that only neat organosiliconliquid (not the pressurized gas from the headspace 614) flows throughthe capillary tube 590. The organosilicon liquid optionally can beheated above ambient temperature, if necessary or desirable to cause theorganosilicon liquid to evaporate, forming an organosilicon vapor.Oxygen is provided from the oxygen tank 594 via an oxygen feed line 596controlled by a mass flow controller 598 and provided with an oxygenshut-off valve 600.

In the apparatus of FIG. 1, the vessel coating station 28 can be, forexample, a PECVD apparatus as further described below, operated undersuitable conditions to deposit a SiO_(x) barrier or other type ofcoating 90 on the interior surface 88 of a vessel 80, as shown in FIG.2.

Referring especially to FIGS. 1 and 2, the processing station 28 caninclude an electrode 160 fed by a radio frequency power supply 162 forproviding an electric field for generating plasma within the vessel 80during processing. In this embodiment, the probe 108 is alsoelectrically conductive and is grounded, thus providing acounter-electrode within the vessel 80. Alternatively, in any embodimentthe outer electrode 160 can be grounded and the probe 108 directlyconnected to the power supply 162.

In the embodiment of FIG. 2, the outer electrode 160 can either begenerally cylindrical as illustrated in FIGS. 2 and 3 or a generallyU-shaped elongated channel. Each illustrated embodiment has one or moresidewalls, such as 164 and 166, and optionally a top end 168, disposedabout the vessel 80 in close proximity.

FIG. 4 shows another variant of the vessel coating station or device 28as previously described. Any one or more of these variants can besubstituted for the vessel coating station or device 28 shown in FIGS.1-2.

FIGS. 11-13 show an array of two or more gas delivery tubes such as 108(also shown in FIG. 2), 510, and 512, which are also inner electrodes.The array can be linear or a carousel.

FIGS. 11-13 also show an inner electrode extender and retractor 514 forinserting and removing the gas delivery tubes/inner electrodes 108, 510,and 512 into and from one or more vessel holders such as 50 or 48. Thesefeatures are optional expedients for using the gas delivery tubes.

In the illustrated embodiment, referring to FIGS. 11-13 as well as 15,the inner electrodes 108, 510, and 512 are respectively connected byflexible hoses 516, 518, and 520 to a common gas supply 144, viashut-off valves 522, 524, and 526. (The flexible hoses are foreshortenedin FIGS. 11-13 by omitting the slack portions). Referring briefly toFIG. 11, the flexible hoses 516, 518, and 520 alternatively can beconnected to independent gas sources 144. A mechanism 514 is provided toextend and retract an inner electrode such as 108. The inner electrodeextender and retractor is configured for moving an inner electrode amonga fully advanced position, an intermediate position, and a retractedposition with respect to the vessel holder.

In FIG. 11, the inner electrode 108 is extended to its operativeposition within the vessel holder 50 and vessel 80, and its shut-offvalve 522 is open. Also in FIG. 11, the idle inner electrodes 510 and512 are retracted and their shut-off valves 524 and 526 are closed. Inthe illustrated embodiment, one or more of the idle inner electrodes 510and 512 are disposed within an electrode cleaning device or station 528.One or more electrodes can be cleaned and others replaced within thestation 528, optionally. The cleaning operations can involve chemicalreaction or solvent treatment to remove deposits, milling to physicallyremove deposits, or plasma treatment to essentially burn awayaccumulated deposits, as non-limiting examples.

In FIG. 12, the idle inner electrodes 510 and 512 are as before, whilethe working inner electrode 108 has been retracted out of the vessel 80,with its distal end remaining within the vessel holder 50, and its valve522 has been closed. In this condition, the vessel 80 can be removed anda new vessel seated on the vessel holder 50 without any danger oftouching the electrode 108 with the vessels 80 being removed andreplaced. After the vessel 80 is replaced, the inner electrode 108 canbe advanced to the position of FIG. 11 and the shut-off valve 522 can bereopened to commence coating the new vessel 80 using the same innerelectrode 108 as before. Thus, in an arrangement in which a series ofthe vessels 80 are seated on and removed from the vessel holder 50, theinner electrode 108 can be extended and partially retracted numeroustimes, as the vessel 80 is installed or removed from the vessel holder50 at the station where the inner electrode 108 is in use

In FIG. 13, the vessel holder 50 and its vessel 80 have been replacedwith a new vessel holder 48 and another vessel 80. Referring to FIG. 1,in this type of embodiment each vessel 80 remains on its vessel holdersuch as 50 or 48 and an inner electrode such as 108 is inserted intoeach vessel as its vessel holder reaches the coating station.

Additionally in FIG. 13, the inner electrode 108 is fully extended andthe electrodes, 510 and 512 are fully retracted, and the array of innerelectrodes 108, 510, and 512 has been moved to the right relative to thevessel holder 48 and electrode cleaning station 528, compared to thepositions of each in FIG. 12, so the inner electrode 108 has been movedout of position and the inner electrode 510 now can be moved intoposition with respect to the vessel holder 48.

It should be understood that the movement of the array of innerelectrodes can be independent of the movement of the vessel holders.They can be moved together or independently, to simultaneously orindependently switch to a new vessel holder and/or a new innerelectrode.

FIGS. 11-13 show an array of two or more gas delivery tubes such as 108(also shown in FIG. 2), 510, and 512, which are also inner electrodes.The array can be linear or a carousel.

FIGS. 11-13 and 16 also show an inner electrode extender and retractor514 for inserting and removing the gas delivery tubes/inner electrodes108, 510, and 512 into and from one or more vessel holders such as 50 or48. These features are optional expedients for using the gas deliverytubes.

In the illustrated embodiment, referring to FIGS. 11-13 and 16, theinner electrodes 108, 510, and 512 are respectively connected byflexible hoses 516, 518, and 520 to a common gas supply 144, viashut-off valves 522, 524, and 526. (The flexible hoses are foreshortenedin FIGS. 11-13 by omitting the slack portions). A mechanism 514 isprovided to extend and retract an inner electrode such as 108. The innerelectrode extender and retractor is configured for moving an innerelectrode among a fully advanced position, an intermediate position, anda retracted position with respect to the vessel holder.

In FIG. 11, the inner electrode 108 is extended to its operativeposition within the vessel holder 50 and vessel 80, and its shut-offvalve 522 is open. Also in FIG. 11, the idle inner electrodes 510 and512 are retracted and their shut-off valves 524 and 526 are closed. Inthe illustrated embodiment, the idle inner electrodes 510 and 512 aredisposed within an electrode cleaning station 528. Some electrodes canbe cleaned and others replaced within the station 528, optionally. Thecleaning operations can involve chemical reaction or solvent treatmentto remove deposits, milling to physically remove deposits, or plasmatreatment to essentially burn away accumulated deposits, as non-limitingexamples.

In FIG. 12, the idle inner electrodes 510 and 512 are as before, whilethe working inner electrode 108 has been retracted out of the vessel 80,with its distal end remaining within the vessel holder 50, and its valve522 has been closed. In this condition, the vessel 80 can be removed anda new vessel seated on the vessel holder 50 without any danger oftouching the electrode 108 with the vessels 80 being removed andreplaced. After the vessel 80 is replaced, the inner electrode 108 canbe advanced to the position of FIG. 11 and the shut-off valve 522 can bereopened to commence coating the new vessel 80 using the same innerelectrode 108 as before. Thus, in an arrangement in which a series ofthe vessels 80 are seated on and removed from the vessel holder 50, theinner electrode 108 can be extended and partially retracted numeroustimes, as the vessel 80 is installed or removed from the vessel holder50 at the station where the inner electrode 108 is in use

In FIG. 13, the vessel holder 50 and its vessel 80 have been replacedwith a new vessel holder 48 and another vessel 80. Referring to FIG. 1,in this type of embodiment each vessel 80 remains on its vessel holdersuch as 50 or 48 and an inner electrode such as 108 is inserted intoeach vessel as its vessel holder reaches the coating station.

Additionally in FIG. 13, the inner electrodes 108, 510, and 512 arefully retracted, and the array of inner electrodes 108, 510, and 512 hasbeen moved to the right relative to the vessel holder 48 and electrodecleaning station 528, compared to the positions of each in FIG. 12, sothe inner electrode 108 has been moved out of position and the innerelectrode 510 has been moved into position with respect to the vesselholder 48.

It should be understood that the movement of the array of innerelectrodes can be independent of the movement of the vessel holders.They can be moved together or independently, to simultaneously orindependently switch to a new vessel holder and/or a new innerelectrode.

An array of two or more inner electrodes 108, 510, and 512 is usefulbecause the individual combined gas delivery tubes/inner electrodes 108,510, and 512 will in some instances tend to accumulate polymerizedreactant gases or some other type of deposits as they are used to coat aseries of vessels such as 80. The deposits can accumulate to the pointat which they detract from the coating rate or uniformity produced,which can be undesirable. To maintain a uniform process, the innerelectrodes can be periodically removed from service, replaced orcleaned, and a new or cleaned electrode can be put into service. Forexample, going from FIG. 11 to FIG. 13, the inner electrode 108 has beenreplaced with a fresh or reconditioned inner electrode 510, which isready to be extended into the vessel holder 48 and the vessel 80 toapply an interior coating to the new vessel.

Thus, an inner electrode drive 530 is operable in conjunction with theinner electrode extender and retractor 514 for removing a first innerelectrode 108 from its extended position to its retracted position,substituting a second inner electrode 510 for the first inner electrode108, and advancing the second inner electrode 510 to its extendedposition (analogous to FIG. 11 except for the substitution ofelectrode).

The array of gas delivery tubes of FIGS. 11-13 and inner electrode drive530 are usable, for example, with the embodiments of FIG. 1-4, 6, or14-16. The extending and retracting mechanism 514 of FIGS. 11-13 isusable, for example, with the gas delivery tube embodiments of FIGS.2-4, 6, 14-16.

The electrode 160 shown in FIG. 2 can be shaped like a “U” channel withits length into the page and the puck or vessel holder 50 can movethrough the activated (powered) electrode during the treatment/coatingprocess. Note that since external and internal electrodes are used, thisapparatus can employ a frequency between 50 Hz and 1 GHz applied from apower supply 162 to the U channel electrode 160. The probe 108 can begrounded to complete the electrical circuit, allowing current to flowthrough the low-pressure gas(es) inside of the vessel 80. The currentcreates plasma to allow the selective treatment and/or coating of theinterior surface 88 of the device.

The electrode in FIG. 2 can also be powered by a pulsed power supply.Pulsing allows for depletion of reactive gases and then removal ofby-products prior to activation and depletion (again) of the reactivegases. Pulsed power systems are typically characterized by their dutycycle which determines the amount of time that the electric field (andtherefore the plasma) is present. The power-on time is relative to thepower-off time. For example a duty cycle of 10% can correspond to apower on time of 10% of a cycle where the power was off for 90% of thetime. As a specific example, the power might be on for 0.1 second andoff for 1 second. Pulsed power systems reduce the effective power inputfor a given power supply 162, since the off-time results in increasedprocessing time. When the system is pulsed, the resulting coating can bevery pure (no byproducts or contaminants). Another result of pulsedsystems is the possibility to achieve atomic layer deposition (ALD). Inthis case, the duty cycle can be adjusted so that the power-on timeresults in the deposition of a single layer of a desired material. Inthis manner, a single atomic layer is contemplated to be deposited ineach cycle. This approach can result in highly pure and highlystructured coatings (although at the temperatures required fordeposition on polymeric surfaces, temperatures optionally are kept low(<100 .degree. C.) and the low-temperature coatings can be amorphous).

PECVD Apparatus Using Gripper for Transporting Tube to and from CoatingStation

Another embodiment is an apparatus for PECVD treatment of a vessel,employing a gripper as previously described. FIG. 4 shows apparatusgenerally indicated at 202 for PECVD treatment of a first vessel 80having an open end 82, a closed end 84, and an interior space defined bythe surface 88. This embodiment includes a vessel holder 48, at least afirst gripper 204 (in this embodiment, for example, a suction cup), aseat defined by the vessel port 92 on the vessel holder 48, a reactantsupply 144, a plasma generator represented by the electrodes 108 and160, a vessel release, which can be a vent valve such as 534, and eitherthe same gripper 204 or a second one (in effect, optionally a secondgripper 204).

The first gripper 204, and as illustrated any of the grippers 204, isconfigured for selectively holding and releasing the closed end 84 of avessel 80. While gripping the closed end 84 of the vessel, the firstgripper 204 can transport the vessel to the vicinity of the vesselholder 48. In the illustrated embodiment, the transportation function isfacilitated by a series conveyor 538 to which the grippers 204 areattached in a series.

The vessel holder 48 has previously been described in connection withother embodiments, and is configured for seating to the open end 82 of avessel 80. The seat defined by the vessel port 92 has previously beendescribed in connection with other embodiments, and is configured forestablishing sealed communication between the vessel holder 48 and theinterior space 88 of the first vessel, and in this case any of thevessels 80. The reactant supply 144 has previously been described inconnection with other embodiments, and is operatively connected forintroducing at least one gaseous reactant within the first vessel 80through the vessel holder 48. The plasma generator defined by theelectrodes 108 and 160 has previously been described in connection withother embodiments, and is configured for forming plasma within the firstvessel under conditions effective to form a reaction product of thereactant on the interior surface of the first vessel.

The vessel release 534 or other expedients, such as introducing withinthe seated vessel 80 a reactant gas, a carrier gas, or an inexpensivegas such as compressed nitrogen or air, can be used for unseating thefirst vessel 80 from the vessel holder 48.

The grippers 204 are configured for axially transporting the firstvessel 80 away from the vessel holder 48 and then releasing the firstvessel 80, as by releasing suction from between the gripper 48 and thevessel end 84.

FIG. 4 also shows a method of PECVD treatment of a first vessel,comprising several steps. A first vessel 80 is provided having an openend 82, a closed end 84, and an interior surface 88. At least a firstgripper 204 is provided that is configured for selectively holding andreleasing the closed end 84 of the first vessel 80. The closed end 84 ofthe first vessel 80 is gripped with the first gripper 204 and therebytransported to the vicinity of a vessel holder 48 configured for seatingto the open end of the first vessel. Next, the first gripper 204 is usedfor axially advancing the first vessel 80 and seating its open end 82 onthe vessel holder 48, establishing sealed communication between thevessel holder 48 and the interior of the first vessel. Next, at leastone gaseous reactant is introduced within the first vessel through thevessel holder, optionally as explained for previous embodiments.

Continuing, plasma is formed within the first vessel under conditionseffective to form a reaction product of the reactant on the interiorsurface of the first vessel, optionally as explained for previousembodiments. The first vessel is unseated from the vessel holder,optionally as explained for previous embodiments. The first gripper oranother gripper is used, optionally as explained for previousembodiments, to axially transport the first vessel away from the vesselholder. The first vessel can then be released from the gripper used toaxially transport it away from the vessel holder, optionally asexplained for previous embodiments.

Further optional steps that can be carried out according to this methodinclude providing a reaction vessel different from the first vessel, thereaction vessel having an open end and an interior space, and seatingthe open end of the reaction vessel on the vessel holder, establishingsealed communication between the vessel holder and the interior space ofthe reaction vessel. A PECVD reactant conduit can be provided within theinterior space. Plasma can be formed within the interior space of thereaction vessel under conditions effective to remove at least a portionof a deposit of a PECVD reaction product from the reactant conduit.These reaction conditions have been explained in connection with apreviously described embodiment. The reaction vessel then can beunseated from the vessel holder and transported away from the vesselholder.

Further optional steps that can be carried out according to anyembodiment of this method include:

-   -   providing at least a second gripper;    -   operatively connecting at least the first and second grippers to        a series conveyor;    -   providing a second vessel having an open end, a closed end, and        an interior surface;    -   providing a gripper configured for selectively holding and        releasing the closed end of the second vessel;    -   gripping the closed end of the second vessel with the gripper;    -   using the gripper, transporting the second vessel to the        vicinity of a vessel holder configured for seating to the open        end of the second vessel;    -   using the gripper, axially advancing the second vessel and        seating its open end on the vessel holder, establishing sealed        communication between the vessel holder and the interior of the        second vessel;    -   introducing at least one gaseous reactant within the second        vessel through the vessel holder;    -   forming plasma within the second vessel under conditions        effective to form a reaction product of the reactant on the        interior surface of the second vessel;    -   unseating the second vessel from the vessel holder; and    -   using the second gripper or another gripper, axially        transporting the second vessel away from the vessel holder; and    -   releasing the second vessel from the gripper used to axially        transport it away from the vessel holder.

FIG. 4 is an example of using a suction cup type device to hold the endof a sample collection tube (in this example) that can move through aproduction line/system. The specific example shown here is one possiblestep (of many possible steps as outlined above and below) ofcoating/treatment. The tube can move into the coating step/area and thetube can be lowered into the vessel holder and (in this example) thecylindrical electrode. The vessel holder, sample collection tube andsuction cup can then move together to the next step where the electrodeis powered and the treatment/coating take place. Any of the above typesof electrodes can be utilized in this example.

Thus, FIG. 4 shows a vessel holder 48 in a coating station 28, employinga vessel transport generally indicated as 202 to move the vessel 80 toand from the coating station 28. The vessel transport 202 can beprovided with a grip 204, which in the illustrated transport 202 can bea suction cup. An adhesive pad, active vacuum source (with a pump todraw air from the grip, actively creating a vacuum) or other expedientcan also be employed as the grip. The vessel transport 202 can be used,for example, to lower the vessel 80 into a seated position in the vesselport 92 to position the vessel 80 for coating. The vessel transport 202can also be used to lift the vessel 80 away from the vessel port 92after processing at the station 28 can be complete. The vessel transport202 also can be used to seat the vessel 80 before the vessel 80 andvessel transport 48 are advanced together to a station. The vesseltransport can also be used to urge the vessel 80 against its seat on thevessel port 92. Also, although FIG. 4 can be oriented to show verticallifting of the vessel 80 from above, an inverted orientation can be orcontemplated in which the vessel transport 202 is below the vessel 80and supports it from beneath.

FIG. 4 shows an embodiment of a method in which vessel transports 202such as suction cups 204 convey the vessels 80 horizontally, as from onestation to the next, as well as (or instead of) vertically into and outof a station such as 28. The vessels 80 can be lifted and transported inany orientation. The illustrated embodiment thus represents a method ofPECVD treatment of a first vessel 80, comprising several steps.

As FIG. 14 for example shows, a reaction vessel 532 different from thefirst vessel 80 can be provided, also having an open end 540 and aninterior space defined by the interior surface 542. Like the vessels 80,the reaction vessel 532 can have its open end 540 on the vessel holder48 and establish sealed communication between the vessel holder 48 andthe interior space 542 of the reaction vessel.

FIG. 14 is a view showing a mechanism for delivering vessels 80 to betreated and a cleaning reactor 532 to a PECVD coating apparatus. In thisembodiment, the inner electrode 108 optionally can be cleaned withoutremoving it from the vessel holder 48.

FIG. 14 shows that the PECVD reactant conduit 108 as previouslydescribed is positioned to be located within the interior space 542 ofthe reaction vessel 532 when the reaction vessel is seated on the vesselholder 48 in place of a vessel 80 which is provided for coating asdescribed previously. FIG. 14 shows the reactant conduit 108 in thisconfiguration, even though the conduit 108 has an exterior portion, aswell as an interior distal end. It suffices for this purpose and thepresent claims if the reactant conduit 108 extends at least partiallyinto the vessel 80 or 532.

The mechanism of FIG. 14 as illustrated is usable with the embodimentsof at least FIGS. 1 and 4, for example. The cleaning reactor 532 canalso be provided as a simple vessel seated and transported on a vesselholder such as 48, in an alternative embodiment. In this configuration,the cleaning reactor 532 can be used with the apparatus of at leastFIGS. 1-3, 6, 11-13, and 15-16, for example.

The plasma generator defined by the electrodes 108 and 160 isconfigurable for forming plasma within the interior space of thereaction vessel 532 under conditions effective to remove at least aportion of a deposit of a PECVD reaction product from the reactantconduit 108. It is contemplated above that the inner electrode and gassource 108 can be a conductive tube, for example a metallic tube, andthat the reaction vessel 532 can be made of any suitable, optionallyheat-resistant material such as ceramic, quartz, glass or othermaterials that can withstand more heat than a thermoplastic vessel. Thematerial of the reaction vessel 532 also can desirably be chemical orplasma resistant to the conditions used in the reaction vessel to removedeposits of reaction products. Optionally, the reaction vessel 532 canbe made of electrically conductive material and itself serve as aspecial-purpose outer electrode for the purpose of removing depositsfrom the reactant conduit 108. As yet another alternative, the reactionvessel 532 can be configured as a cap that seats on the outer electrode160, in which case the outer electrode 160 would optionally be seated onthe vessel holder 48 to define a closed cleaning reaction chamber.

It is contemplated that the reaction conditions effective to remove atleast a portion of a deposit of a PECVD reaction product from thereactant conduit 108 include introduction of a substantial portion of anoxidizing reactant such as oxygen or ozone (either generated separatelyor by the plasma apparatus), a higher power level than is used fordeposition of coatings, a longer cycle time than is used for depositionof coatings, or other expedients known for removing the type of unwanteddeposit encountered on the reaction conduit 108. For another example,mechanical milling can also be used to remove unwanted deposits. Or,solvents or other agents can be forced through the reactant conduit 108to clear obstructions. These conditions can be far more severe than whatthe vessels 80 to be coated can withstand, since the reaction vessel 532does not need to be suitable for the normal uses of the vessel 80.Optionally, however, a vessel 80 can be used as the reaction vessel, andif the deposit removing conditions are too severe the vessel 80 employedas a reaction vessel can be discarded, in an alternative embodiment.

PECVD Methods for Making Vessels

Precursors for PECVD Coating

The precursor for the PECVD coating of the present invention is broadlydefined as an organometallic precursor. An organometallic precursor isdefined in this specification as comprehending compounds of metalelements from Group III and/or Group IV of the Periodic Table havingorganic residues, e.g. hydrocarbon, aminocarbon or oxycarbon residues.Organometallic compounds as presently defined include any precursorhaving organic moieties bonded to silicon or other Group III/IV metalatoms directly, or optionally bonded through oxygen or nitrogen atoms.The relevant elements of Group III of the Periodic Table are Boron,Aluminum, Gallium, Indium, Thallium, Scandium, Yttrium, and Lanthanum,Aluminum and Boron being preferred. The relevant elements of Group IV ofthe Periodic Table are Silicon, Germanium, Tin, Lead, Titanium,Zirconium, Hafnium, and Thorium, with Silicon and Tin being preferred.Other volatile organic compounds can also be contemplated. However,organosilicon compounds are preferred for performing present invention.

An organosilicon precursor is contemplated, where an “organosiliconprecursor” is defined throughout this specification most broadly as acompound having at least one of the linkages:

-   -   or

The first structure immediately above is a tetravalent silicon atomconnected to an oxygen atom and an organic carbon atom (an organiccarbon atom being a carbon atom bonded to at least one hydrogen atom).The second structure immediately above is a tetravalent silicon atomconnected to an —NH— linkage and an organic carbon atom (an organiccarbon atom being a carbon atom bonded to at least one hydrogen atom).Optionally, the organosilicon precursor is selected from the groupconsisting of a linear siloxane, a monocyclic siloxane, a polycyclicsiloxane, a polysilsesquioxane, a linear silazane, a monocyclicsilazane, a polycyclic silazane, a polysilsesquiazane, and a combinationof any two or more of these precursors. Also contemplated as aprecursor, though not within the two formulas immediately above, is analkyl trimethoxysilane.

If an oxygen-containing precursor (e.g. a siloxane) is used, arepresentative predicted empirical composition resulting from PECVDunder conditions forming a lubricating coating would beSi_(w)O_(x)C_(y)H_(z) as defined in the Definition Section, while arepresentative predicted empirical composition resulting from PECVDunder conditions forming a barrier layer would be SiO_(x), where x inthis formula is from about 1.5 to about 2.9. If a nitrogen-containingprecursor (e.g. a silazane) is used, the predicted composition would beSi_(w)*N_(x)*C_(y)*H_(z)*, i.e. in Si_(w)O_(x)C_(y)H_(z) as specified inthe Definition Section, O is replaced by N and the indices are adaptedto the higher valency of N as compared to O (3 instead of 2). The latteradaptation will generally follow the ratio of w, x, y and z in asiloxane to the corresponding indices in its aza counterpart. In aparticular aspect of the invention, Si_(w)*N_(x)*C_(y)*H_(z)* in whichw*, x*, y*, and z* are defined the same as w, x, y, and z for thesiloxane counterparts, but for an optional deviation in the number ofhydrogen atoms.

One type of precursor starting material having the above empiricalformula is a linear siloxane, for example a material having thefollowing formula:

in which each R is independently selected from alkyl, for examplemethyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, vinyl,alkyne, or others, and n is 1, 2, 3, 4, or greater, optionally two orgreater. Several examples of contemplated linear siloxanes arehexamethyldisiloxane (HMDSO), octamethyltrisiloxane,decamethyltetrasiloxane, dodecamethylpentasiloxane, or combinations oftwo or more of these. The analogous silazanes in which —NH— issubstituted for the oxygen atom in the above structure are also usefulfor making analogous coatings. Several examples of contemplated linearsilazanes are octamethyltrisilazane, decamethyltetrasilazane, orcombinations of two or more of these.

Another type of precursor starting material is a monocyclic siloxane,for example a material having the following structural formula:

in which R is defined as for the linear structure and “a” is from 3 toabout 10, or the analogous monocyclic silazanes. Several examples ofcontemplated hetero-substituted and unsubstituted monocyclic siloxanesand silazanes include

-   -   1,3,5-trimethyl-1,3,5-tris(3,3,3-trifluoropropyl)methyl]cyclotrisiloxane    -   2,4,6,8-tetramethyl-2,4,6,8-tetravinylcyclotetrasiloxane,    -   pentamethylcyclopentasiloxane,    -   pentavinylpentamethylcyclopentasiloxane,    -   hexamethylcyclotrisiloxane,    -   hexaphenylcyclotrisiloxane,    -   octamethylcyclotetrasiloxane (OMCTS),    -   octaphenylcyclotetrasiloxane,    -   decamethylcyclopentasiloxane    -   dodecamethylcyclohexasiloxane,    -   methyl(3,3,3-trifluoropropl)cyclosiloxane,    -   Cyclic organosilazanes are also contemplated, such as    -   Octamethylcyclotetrasilazane,    -   1,3,5,7-tetravinyl-1,3,5,7-tetramethylcyclotetrasilazane        hexamethylcyclotrisilazane,    -   octamethylcyclotetrasilazane,    -   decamethylcyclopentasilazane,    -   dodecamethylcyclohexasilazane, or combinations of any two or        more of these.

Another type of precursor starting material is a polycyclic siloxane,for example a material having one of the following structural formulas:

in which Y can be oxygen or nitrogen, E is silicon, and Z is a hydrogenatom or an organic substituent, for example alkyl such as methyl, ethyl,propyl, isopropyl, butyl, isobutyl, t-butyl, vinyl, alkyne, or others.When each Y is oxygen, the respective structures, from left to right,are a silatrane, a silquasilatrane, and a silproatrane. When Y isnitrogen, the respective structures are an azasilatrane, anazasilquasiatrane, and an azasilproatrane.

Another type of polycyclic siloxane precursor starting material is apolysilsesquioxane, with the empirical formula RSiO_(1.5) and thestructural formula shown as a T₈ cube:

in which each R is a hydrogen atom or an organic substituent, forexample alkyl such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl,t-butyl, vinyl, alkyne, or others. Two commercial materials of this sortare a T₈ cube, available as a commercial product SST-eM01poly(methylsilsesquioxane), in which each R is methyl, and another T₈cube, available as a commercial product SST-3 MH1.1poly(Methyl-Hydridosilsesquioxane), in which 90% of the R groups aremethyl, 10% are hydrogen atoms. This material is available in a 10%solution in tetrahydrofuran, for example. Combinations of two or more ofthese are also contemplated. Other examples of a contemplated precursorare methylsilatrane, CAS No. 2288-13-3, in which each Y is oxygen and Zis methyl, methylazasilatrane, or a combination of any two or more ofthese.

The analogous polysilsesquiazanes in which —NH— is substituted for theoxygen atom in the above structure are also useful for making analogouscoatings. Examples of contemplated polysilsesquiazanes are apoly(methylsilsesquiazane), in which each R is methyl, and apoly(Methyl-Hydridosilsesquiazane, in which 90% of the R groups aremethyl, 10% are hydrogen atoms. Combinations of two or more of these arealso contemplated.

One particularly contemplated precursor for the lubricity layeraccording to the present invention is a monocyclic siloxane, for exampleis octamethylcyclotetrasiloxane.

One particularly contemplated precursor for the barrier layer accordingto the present invention is a linear siloxane, for example is HMDSO.

In any of the coating methods according to the present invention, theapplying step optionally can be carried out by vaporizing the precursorand providing it in the vicinity of the substrate. E.g., OMCTS isusually vaporized by heating it to about 50 .degree. C. before applyingit to the PECVD apparatus.

General PECVD Method

In the context of the present invention, the following PECVD method isgenerally applied, which contains the following steps:

(a) providing a gaseous reactant comprising a precursor as definedherein, optionally an organosilicon precursor, and optionally O₂ in thevicinity of the substrate surface; and

(b) generating plasma from the gaseous reactant, thus forming a coatingon the substrate surface by plasma enhanced chemical vapor deposition(PECVD).

In the method, the coating characteristics are advantageously set by oneor more of the following conditions: the plasma properties, the pressureunder which the plasma is applied, the power applied to generate theplasma, the presence and relative amount of O₂ in the gaseous reactant,the plasma volume, and the organosilicon precursor. Optionally, thecoating characteristics are set by the presence and relative amount ofO₂ in the gaseous reactant and/or the power applied to generate theplasma.

In all embodiments of the present invention, the plasma is in anoptional aspect a non-hollow-cathode plasma.

In a further preferred aspect, the plasma is generated at reducedpressure (as compared to the ambient or atmospheric pressure).Optionally, the reduced pressure is less than 300 mTorr, optionally lessthan 200 mTorr, even optionally less than 100 mTorr.

The PECVD optionally is performed by energizing the gaseous reactantcontaining the precursor with electrodes powered at a frequency atmicrowave or radio frequency, and optionally at a radio frequency. Theradio frequency preferred to perform an embodiment of the invention willalso be addressed as “RF frequency”. A typical radio frequency range forperforming the present invention is a frequency of from 10 kHz to lessthan 300 MHz, optionally from 1 to 50 MHz, even optionally from 10 to 15MHz. A frequency of 13.56 MHz is most preferred, this being a governmentsanctioned frequency for conducting PECVD work.

There are several advantages for using a RF power source versus amicrowave source: Since RF operates a lower power, there is less heatingof the substrate/vessel. Because the focus of the present invention isputting a plasma coating on plastic substrates, lower processingtemperature are desired to prevent melting/distortion of the substrate.To prevent substrate overheating when using microwave PECVD, themicrowave PECVD is applied in short bursts, by pulsing the power. Thepower pulsing extends the cycle time for the coating, which is undesiredin the present invention. The higher frequency microwave can also causeoffgassing of volatile substances like residual water, oligomers andother materials in the plastic substrate. This offgassing can interferewith the PECVD coating. A major concern with using microwave for PECVDis delamination of the coating from the substrate. Delamination occursbecause the microwaves change the surface of the substrate prior todepositing the coating layer. To mitigate the possibility ofdelamination, interface coating layers have been developed for microwavePECVD to achieve good bonding between the coating and the substrate.Finally, the lubricity layers according to the present invention areadvantageously applied using lower power. RF power operates at lowerpower and provides more control over the PECVD process than microwavepower. Nonetheless, microwave power, though less preferred, is usableunder suitable process conditions.

Furthermore, for all PECVD methods described herein, there is a specificcorrelation between the power (in Watts) used to generate the plasma andthe volume of the lumen wherein the plasma is generated. Typically, thelumen is the lumen of a vessel coated according to the presentinvention. The RF power should scale with the volume of the vessel ifthe same electrode system is employed. Once the composition of a gaseousreactant, for example the ratio of the precursor to O₂, and all otherparameters of the PECVD coating method but the power have been set, theywill typically not change when the geometry of a vessel is maintainedand only its volume is varied. In this case, the power will be directlyproportional to the volume. Thus, starting from the power to volumeratios provided by present description, the power which has to beapplied in order to achieve the same or a similar coating in a vessel ofsame geometry, but different size, can easily be found. The influence ofthe vessel geometry on the power to be applied is illustrated by theresults of the Examples for tubes in comparison to the Examples forsyringe barrels.

For any coating of the present invention, the plasma is generated withelectrodes powered with sufficient power to form a coating on thesubstrate surface. For a lubricity layer, in the method according to anembodiment of the invention the plasma is optionally generated (i) withelectrodes supplied with an electric power of from 0.1 to 25 W,optionally from 1 to 22 W, optionally from 3 to 17 W, even optionallyfrom 5 to 14 W, optionally from 7 to 11 W, for example of 8 W; and/or(ii) wherein the ratio of the electrode power to the plasma volume isless than 10 W/ml, optionally is from 5 W/ml to 0.1 W/ml, optionally isfrom 4 W/ml to 0.1 W/ml, optionally from 2 W/ml to 0.2 W/ml. For abarrier layer or SiO_(x) coating, the plasma is optionally generated (i)with electrodes supplied with an electric power of from 8 to 500 W,optionally from 20 to 400 W, optionally from 35 to 350 W, evenoptionally from 44 to 300 W, optionally from 44 to 70 W; and/or (ii) theratio of the electrode power to the plasma volume is equal or more than5 W/ml, optionally is from 6 W/ml to 150 W/ml, optionally is from 7 W/mlto 100 W/ml, optionally from 7 W/ml to 20 W/ml.

The vessel geometry can also influence the choice of the gas inlet usedfor the PECVD coating. In a particular aspect, a syringe can be coatedwith an open tube inlet, and a tube can be coated with a gas inlethaving small holes which is extended into the tube.

The power (in Watts) used for PECVD also has an influence on the coatingproperties. Typically, an increase of the power will increase thebarrier properties of the coating, and a decrease of the power willincrease the lubricity of the coating. E.g., for a coating on the innerwall of syringe barrel having a volume of about 3 ml, a power of lessthan 30 W will lead to a coating which is predominantly a barrier layer,while a power of more than 30 W will lead to a coating which ispredominantly a lubricity layer (see Examples).

A further parameter determining the coating properties is the ratio ofO₂ (or another oxidizing agent) to the precursor (e.g. organosiliconprecursor) in the gaseous reactant used for generating the plasma.Typically, an increase of the O₂ ratio in the gaseous reactant willincrease the barrier properties of the coating, and a decrease of the O₂ratio will increase the lubricity of the coating.

If a lubricity layer is desired, then O₂ is optionally present in avolume-volume ratio to the gaseous reactant of from 0:1 to 5:1,optionally from 0:1 to 1:1, even optionally from 0:1 to 0.5:1 or evenfrom 0:1 to 0.1:1. Most advantageously, essentially no oxygen is presentin the gaseous reactant. Thus, the gaseous reactant will in someembodiments comprise less than 1 vol % O₂, for example less than 0.5 vol% O₂, and optionally is O₂-free.

If, on the other hand, a barrier or SiO_(x) coating is desired, then theO₂ is optionally present in a volume:volume ratio to the gaseousreactant of from 1:1 to 100:1 in relation to the silicon containingprecursor, optionally in a ratio of from 5:1 to 30:1, optionally in aratio of from 10:1 to 20:1, even optionally in a ratio of 15:1.

PECVD to Apply SiO_(x) Barrier Layer, Using Plasma that is SubstantiallyFree of Hollow Cathode Plasma

A specific embodiment is a method of applying a barrier layer ofSiO_(x), defined in this specification (unless otherwise specified in aparticular instance) as a coating containing silicon, oxygen, andoptionally other elements, in which x, the ratio of oxygen to siliconatoms, is from about 1.5 to about 2.9, or 1.5 to about 2.6, or about 2.These alternative definitions of x apply to any use of the term SiO_(x)in this specification. The barrier layer is applied to the interior of avessel, for example a sample collection tube, a syringe barrel, oranother type of vessel. The method includes several steps.

A vessel wall is provided, as is a reaction mixture comprising plasmaforming gas, i.e. an organosilicon compound gas, optionally an oxidizinggas, and optionally a hydrocarbon gas.

Plasma is formed in the reaction mixture that is substantially free ofhollow cathode plasma. The vessel wall is contacted with the reactionmixture, and the coating of SiO_(x) is deposited on at least a portionof the vessel wall.

In certain embodiments, the generation of a uniform plasma throughoutthe portion of the vessel to be coated is contemplated, as it has beenfound in certain instances to generate an SiO_(x) coating providing abetter barrier against oxygen. Uniform plasma means regular plasma thatdoes not include a substantial amount of hollow cathode plasma (whichhas a higher emission intensity than regular plasma and is manifested asa localized area of higher intensity interrupting the more uniformintensity of the regular plasma).

The hollow cathode effect is generated by a pair of conductive surfacesopposing each other with the same negative potential with respect to acommon anode. If the spacing is made (depending on the pressure and gastype) such that the space charge sheaths overlap, electrons start tooscillate between the reflecting potentials of the opposite wall sheathsleading to multiple collisions as the electrons are accelerated by thepotential gradient across the sheath region. The electrons are confinedin the space charge sheath overlap which results in very high ionizationand high ion density plasmas. This phenomenon is described as the hollowcathode effect. Those skilled in the art are able to vary the processingconditions, such as the power level and the feed rates or pressure ofthe gases, to form uniform plasma throughout or to form plasma includingvarious degrees of hollow cathode plasma.

The inventors have found that the uniformity of coating can be improvedin certain embodiments by repositioning the distal end of the electrode308 relative to the vessel 250 so it does not penetrate as far into thelumen 300 of the vessel 250 as the position of the inner electrode shownin previous Figures. For example, although in certain embodiments thedistal opening 316 can be positioned adjacent to the restricted opening294, in other embodiments the distal opening 316 can be positioned lessthan ⅞ the distance, optionally less than ¾ the distance, optionallyless than half the distance to the restricted opening 294 from thelarger opening 302 of the vessel to be processed while feeding thereactant gas. Or, the distal opening 316 can be positioned less than40%, less than 30%, less than 20%, less than 15%, less than 10%, lessthan 8%, less than 6%, less than 4%, less than 2%, or less than 1% ofthe distance to the restricted opening 294 from the larger opening ofthe vessel to be processed while feeding the reactant gas.

Or, the distal end of the electrode 308 can be positioned eitherslightly inside or outside or flush with the larger opening 302 of thevessel 250 to be processed while communicating with, and feeding thereactant gas to, the interior of the vessel 250. The positioning of thedistal opening 316 relative to the vessel 250 to be processed can beoptimized for particular dimensions and other conditions of treatment bytesting it at various positions. One particular position of theelectrode 308 contemplated for treating syringe barrels 250 is with thedistal end 314 penetrating about a quarter inch (about 6 mm) into thevessel lumen 300 above the larger opening 302.

The inventors presently contemplate that it is advantageous to place atleast the distal end 314 of the electrode 308 within the vessel 250 soit will function suitably as an electrode, though that is notnecessarily a requirement. Surprisingly, the plasma 318 generated in thevessel 250 can be made more uniform, extending through the restrictedopening 294 into the processing vessel lumen 304, with less penetrationof the electrode 308 into the lumen 300 than has previously beenemployed. With other arrangements, such as processing a closed-endedvessel, the distal end 314 of the electrode 308 commonly is placedcloser to the closed end of the vessel than to its entrance.

Or, the distal end 314 of the electrode 308 can be positioned at therestricted opening 294 or beyond the restricted opening 294, for examplewithin the processing vessel lumen 304. Various expedients canoptionally be provided, such as shaping the processing vessel 296 toimprove the gas flow through the restricted opening 294.

In yet another contemplated embodiment, the inner electrode 160 as inFIG. 2 can be moved during processing, for example, at first extendinginto the processing vessel lumen, then being withdrawn progressivelyproximally as the process proceeds. This expedient is particularlycontemplated if the vessel 250, under the selected processingconditions, is long, and movement of the inner electrode facilitatesmore uniform treatment of the interior surface 254. Using thisexpedient, the processing conditions, such as the gas feed rate, thevacuum draw rate, the electrical energy applied to the outer electrode160, the rate of withdrawing the inner electrode 160, or other factorscan be varied as the process proceeds, customizing the process todifferent parts of a vessel to be treated.

Method of Applying a Lubricity Layer

Another embodiment is a method of applying a lubricity layer derivedfrom an organosilicon precursor. A “lubricity layer” or any similar termis generally defined as a coating that reduces the frictional resistanceof the coated surface, relative to the uncoated surface. If the coatedobject is a syringe (or syringe part, e.g. syringe barrel) or any otheritem generally containing a plunger or movable part in sliding contactwith the coated surface, the frictional resistance has two mainaspects—breakout force and plunger sliding force.

The plunger sliding force test is a specialized test of the coefficientof sliding friction of the plunger within a syringe, accounting for thefact that the normal force associated with a coefficient of slidingfriction as usually measured on a flat surface is addressed bystandardizing the fit between the plunger or other sliding element andthe tube or other vessel within which it slides. The parallel forceassociated with a coefficient of sliding friction as usually measured iscomparable to the plunger sliding force measured as described in thisspecification. Plunger sliding force can be measured, for example, asprovided in the ISO 7886-1:1993 test.

The plunger sliding force test can also be adapted to measure othertypes of frictional resistance, for example the friction retaining astopper within a tube, by suitable variations on the apparatus andprocedure. In one embodiment, the plunger can be replaced by a closureand the withdrawing force to remove or insert the closure can bemeasured as the counterpart of plunger sliding force.

Also or instead of the plunger sliding force, the breakout force can bemeasured. The breakout force is the force required to start a stationaryplunger moving within a syringe barrel, or the comparable force requiredto unseat a seated, stationary closure and begin its movement. Thebreakout force is measured by applying a force to the plunger thatstarts at zero or a low value and increases until the plunger beginsmoving. The breakout force tends to increase with storage of a syringe,after the prefilled syringe plunger has pushed away the interveninglubricant or adhered to the barrel due to decomposition of the lubricantbetween the plunger and the barrel. The breakout force is the forceneeded to overcome “sticktion,” an industry term for the adhesionbetween the plunger and barrel that needs to be overcome to break outthe plunger and allow it to begin moving.

Some utilities of coating a vessel in whole or in part with a lubricitylayer, such as selectively at surfaces contacted in sliding relation toother parts, is to ease the insertion or removal of a stopper or passageof a sliding element such as a piston in a syringe or a stopper in asample tube. The vessel can be made of glass or a polymer material suchas polyester, for example polyethylene terephthalate (PET), a cyclicolefin copolymer (COC), an olefin such as polypropylene, or othermaterials. Applying a lubricity layer by PECVD can avoid or reduce theneed to coat the vessel wall or closure with a sprayed, dipped, orotherwise applied organosilicon or other lubricant that commonly isapplied in a far larger quantity than would be deposited by a PECVDprocess.

In any of the present embodiments, a plasma, optionally anon-hollow-cathode plasma, optionally can be formed in the vicinity ofthe substrate

In any of the present embodiments, the precursor optionally can beprovided in the substantial absence of oxygen. In any of the presentembodiments, the precursor optionally can be provided in the substantialabsence of a carrier gas. In any of the present embodiments, theprecursor optionally can be provided in the substantial absence ofnitrogen. In any of the present embodiments, the precursor optionallycan be provided at less than 1 Torr absolute pressure.

In any of the present embodiments, the precursor optionally can beprovided to the vicinity of a plasma emission.

In any of the present embodiments, the coating optionally can be appliedto the substrate at a thickness of 1 to 5000 nm, or 10 to 1000 nm, or10-200 nm, or 20 to 100 nm thick. The thickness of this and othercoatings can be measured, for example, by transmission electronmicroscopy (TEM).

The TEM can be carried out, for example, as follows. Samples can beprepared for Focused Ion Beam (FIB) cross-sectioning in two ways. Eitherthe samples can be first coated with a thin layer of carbon (50-100 nmthick) and then coated with a sputtered layer of platinum (50-100 nmthick) using a K575X Emitech coating system, or the samples can becoated directly with the protective sputtered Pt layer. The coatedsamples can be placed in an FEI FIB200 FIB system. An additional layerof platinum can be FIB-deposited by injection of an oregano-metallic gaswhile rastering the 30 kV gallium ion beam over the area of interest.The area of interest for each sample can be chosen to be a location halfway down the length of the syringe barrel. Thin cross sections measuringapproximately 15 .mu.m (“micrometers”) long, 2 .mu.m wide and 15 .mu.mdeep can be extracted from the die surface using a proprietary in-situFIB lift-out technique. The cross sections can be attached to a 200 meshcopper TEM grid using FIB-deposited platinum. One or two windows in eachsection, measuring .about.8 .mu.m wide, can be thinned to electrontransparency using the gallium ion beam of the FEI FIB.

Cross-sectional image analysis of the prepared samples can be performedutilizing either a Transmission Electron Microscope (TEM), or a ScanningTransmission Electron Microscope (STEM), or both. All imaging data canbe recorded digitally. For STEM imaging, the grid with the thinned foilscan be transferred to a Hitachi HD2300 dedicated STEM. Scanningtransmitted electron images can be acquired at appropriatemagnifications in atomic number contrast mode (ZC) and transmittedelectron mode (TE). The following instrument settings can be used.

Scanning Transmission Instrument Electron Microscope Manufacturer/ModelHitachi HD2300 Accelerating Voltage 200 kV Objective Aperture #2Condenser Lens 1 Setting 1.672 Condenser Lens 2 Setting 1.747Approximate Objective Lens Setting 5.86 ZC Mode Projector Lens 1.149 TEMode Projector Lens 0.7 Image Acquisition Pixel Resolution 1280 × 960Acquisition Time 20 sec.(×4)

For TEM analysis the sample grids can be transferred to a Hitachi HF2000transmission electron microscope. Transmitted electron images can beacquired at appropriate magnifications. The relevant instrument settingsused during image acquisition can be those given below.

Transmission Instrument Electron Microscope Manufacturer/Model HitachiHF2000 Accelerating Voltage 200 kV Condenser Lens 1 0.78 Condenser Lens2 0 Objective Lens 6.34 Condenser Lens Aperture #1 Objective LensAperture for #3 imaging Selective Area Aperture for SAD N/A

In any of the present embodiments, the substrate can comprise glass or apolymer, for example a polycarbonate polymer, an olefin polymer, acyclic olefin copolymer, a polypropylene polymer, a polyester polymer, apolyethylene terephthalate polymer or a combination of any two or moreof these.

In any of the present embodiments, the PECVD optionally can be performedby energizing the gaseous reactant containing the precursor withelectrodes powered at a RF frequency as defined above, for example afrequency from 10 kHz to less than 300 MHz, optionally from 1 to 50 MHz,even optionally from 10 to 15 MHz, optionally a frequency of 13.56 MHz.

In any of the present embodiments, the plasma can be generated byenergizing the gaseous reactant comprising the precursor with electrodessupplied with electric power sufficient to form a lubricity layer.Optionally, the plasma is generated by energizing the gaseous reactantcontaining the precursor with electrodes supplied with an electric powerof from 0.1 to 25 W, optionally from 1 to 22 W, optionally from 3 to 17W, even optionally from 5 to 14 W, optionally from 7 to 11 W, optionally8 W. The ratio of the electrode power to the plasma volume can be lessthan 10 W/ml, optionally is from 5 W/ml to 0.1 W/ml, optionally is from4 W/ml to 0.1 W/ml, optionally from 2 W/ml to 0.2 W/ml. These powerlevels are suitable for applying lubricity coatings to syringes andsample tubes and vessels of similar geometry having a void volume of 1to 3 mL in which PECVD plasma is generated. It is contemplated that forlarger or smaller objects the power applied should be increased orreduced accordingly to scale the process to the size of the substrate.

One contemplated product optionally can be a syringe having a barreltreated by the method of any one or more of embodiments

Liquid-Applied Coatings

Another example of a suitable barrier or other type of coating, usablein conjunction with PECVD-applied coatings or other PECVD treatment asdisclosed here, can be a liquid barrier, lubricant, or other type ofcoating 90 applied to the interior surface of a vessel, either directlyor with one or more intervening PECVD-applied coatings described in thisspecification, for example SiO_(x), a lubricity layer characterized asdefined in the Definition Section, or both.

Suitable liquid barriers or other types of coatings 90 also optionallycan be applied, for example, by applying a liquid monomer or otherpolymerizable or curable material to the interior surface of the vessel80 and curing, polymerizing, or crosslinking the liquid monomer to forma solid polymer. Suitable liquid barrier or other types of coatings 90can also be provided by applying a solvent-dispersed polymer to thesurface 88 and removing the solvent.

Either of the above methods can include as a step forming a coating 90on the interior 88 of a vessel 80 via the vessel port 92 at a processingstation or device 28. One example is applying a liquid coating, forexample of a curable monomer, prepolymer, or polymer dispersion, to theinterior surface 88 of a vessel 80 and curing it to form a film thatphysically isolates the contents of the vessel 80 from its interiorsurface 88. The prior art describes polymer coating technology assuitable for coating plastic blood collection tubes. For example, theacrylic and polyvinylidene chloride (PVdC) coating materials and coatingmethods described in U.S. Pat. No. 6,165,566, which is herebyincorporated by reference, optionally can be used.

Either of the above methods can also or include as a step forming acoating on the exterior outer wall of a vessel 80. The coatingoptionally can be a barrier layer, optionally an oxygen barrier layer,or optionally a water barrier layer. One example of a suitable coatingis polyvinylidene chloride, which functions both as a water barrier andan oxygen barrier. Optionally, the barrier layer can be applied as awater-based coating. The coating optionally can be applied by dippingthe vessel in it, spraying it on the vessel, or other expedients. Avessel having an exterior barrier layer as described above is alsocontemplated.

PECVD Treated Vessels

Vessels are contemplated having a barrier layer 90 (shown in FIG. 2, forexample), which can be an coating applied to a thickness of at least 2nm, or at least 4 nm, or at least 7 nm, or at least 10 nm, or at least20 nm, or at least 30 nm, or at least 40 nm, or at least 50 nm, or atleast 100 nm, or at least 150 nm, or at least 200 nm, or at least 300nm, or at least 400 nm, or at least 500 nm, or at least 600 nm, or atleast 700 nm, or at least 800 nm, or at least 900 nm. The coating can beup to 1000 nm, or at most 900 nm, or at most 800 nm, or at most 700 nm,or at most 600 nm, or at most 500 nm, or at most 400 nm, or at most 300nm, or at most 200 nm, or at most 100 nm, or at most 90 nm, or at most80 nm, or at most 70 nm, or at most 60 nm, or at most 50 nm, or at most40 nm, or at most 30 nm, or at most 20 nm, or at most 10 nm, or at most5 nm thick. Specific thickness ranges composed of any one of the minimumthicknesses expressed above, plus any equal or greater one of themaximum thicknesses expressed above, are expressly contemplated. Thethickness of the SiO_(x) or other coating can be measured, for example,by transmission electron microscopy (TEM), and its composition can bemeasured by X-ray photoelectron spectroscopy (XPS).

It is contemplated that the choice of the material to be barred frompermeating the coating and the nature of the SiO_(x) coating applied canaffect its barrier efficacy. For example, two examples of materialcommonly intended to be barred are oxygen and water/water vapor.Materials commonly are a better barrier to one than to the other. Thisis believed to be so at least in part because oxygen is transmittedthrough the coating by a different mechanism than water is transmitted.

Oxygen transmission is affected by the physical features of the coating,such as its thickness, the presence of cracks, and other physicaldetails of the coating. Water transmission, on the other hand, isbelieved to commonly be affected by chemical factors, i.e. the materialof which the coating is made, more than physical factors. The inventorsalso believe that at least one of these chemical factors is asubstantial concentration of OH moieties in the coating, which leads toa higher transmission rate of water through the barrier. An SiO_(x)coating often contains OH moieties, and thus a physically sound coatingcontaining a high proportion of OH moieties is a better barrier tooxygen than to water. A physically sound carbon-based barrier, such asamorphous carbon or diamond-like carbon (DLC) commonly is a betterbarrier to water than is an SiO_(x) coating because the carbon-basedbarrier more commonly has a lower concentration of OH moieties.

Other factors lead to a preference for an SiO_(x) coating, however, suchas its oxygen barrier efficacy and its close chemical resemblance toglass and quartz. Glass and quartz (when used as the base material of avessel) are two materials long known to present a very high barrier tooxygen and water transmission as well as substantial inertness to manymaterials commonly carried in vessels. Thus, it is commonly desirable tooptimize the water barrier properties such as the water vaportransmission rate (WVTR) of an SiO_(x) coating, rather than choosing adifferent or additional type of coating to serve as a water transmissionbarrier.

Several ways contemplated to improve the WVTR of an SiO_(x) coating areas follow.

The concentration ratio of organic moieties (carbon and hydrogencompounds) to OH moieties in the deposited coating can be increased.This can be done, for example, by increasing the proportion of oxygen inthe feed gases (as by increasing the oxygen feed rate or by lowering thefeed rate of one or more other constituents). The lowered incidence ofOH moieties is believed to result from increasing the degree of reactionof the oxygen feed with the hydrogen in the silicone source to yieldmore volatile water in the PECVD exhaust and a lower concentration of OHmoieties trapped or incorporated in the coating.

Higher energy can be applied in the PECVD process, either by raising theplasma generation power level, by applying the power for a longerperiod, or both. An increase in the applied energy must be employed withcare when used to coat a plastic tube or other device, as it also has atendency to distort the vessel being treated, to the extent the tubeabsorbs the plasma generation power. This is why RF power iscontemplated in the context of present application. Distortion of themedical devices can be reduced or eliminated by employing the energy ina series of two or more pulses separated by cooling time, by cooling thevessels while applying energy, by applying the coating in a shorter time(commonly thus making it thinner), by selecting a frequency of theapplied coating that is absorbed minimally by the base material selectedfor being coated, and/or by applying more than one coating, with time inbetween the respective energy application steps. For example, high powerpulsing can be used with a duty cycle of 1 millisecond on, 99milliseconds off, while continuing to feed the process gas. The processgas is then the coolant, as it keeps flowing between pulses. Anotheralternative is to reconfigure the power applicator, as by adding magnetsto confine the plasma increase the effective power application (thepower that actually results in incremental coating, as opposed to wastepower that results in heating or unwanted coating). This expedientresults in the application of more coating-formation energy per totalWatt-hour of energy applied. See for example U.S. Pat. No. 5,904,952.

An oxygen post-treatment of the coating can be applied to remove OHmoieties from the previously-deposited coating. This treatment is alsocontemplated to remove residual volatile organosilicon compounds orsilicones or oxidize the coating to form additional SiO_(x).

The plastic base material tube can be preheated.

A different volatile source of silicon, such as hexamethyldisilazane(HMDZ), can be used as part or all of the silicone feed. It iscontemplated that changing the feed gas to HMDZ will address the problembecause this compound has no oxygen moieties in it, as supplied. It iscontemplated that one source of OH moieties in the HMDSO-sourced coatingis hydrogenation of at least some of the oxygen atoms present inunreacted HMDSO.

A composite coating can be used, such as a carbon-based coating combinedwith SiO_(x). This can be done, for example, by changing the reactionconditions or by adding a substituted or unsubstituted hydrocarbon, suchas an alkane, alkene, or alkyne, to the feed gas as well as anorganosilicon-based compound. See for example U.S. Pat. No. 5,904,952,which states in relevant part: “For example, inclusion of a lowerhydrocarbon such as propylene provides carbon moieties and improves mostproperties of the deposited films (except for light transmission), andbonding analysis indicates the film to be silicon dioxide in nature. Useof methane, methanol, or acetylene, however, produces films that aresilicone in nature. The inclusion of a minor amount of gaseous nitrogento the gas stream provides nitrogen moieties in the deposited films andincreases the deposition rate, improves the transmission and reflectionoptical properties on glass, and varies the index of refraction inresponse to varied amounts of N₂. The addition of nitrous oxide to thegas stream increases the deposition rate and improves the opticalproperties, but tends to decrease the film hardness.”

A diamond-like carbon (DLC) coating can be formed as the primary or solecoating deposited. This can be done, for example, by changing thereaction conditions or by feeding methane, hydrogen, and helium to aPECVD process. These reaction feeds have no oxygen, so no OH moietiescan be formed. For one example, an SiO_(x) coating can be applied on theinterior of a tube or syringe barrel and an outer DLC coating can beapplied on the exterior surface of a tube or syringe barrel. Or, theSiO_(x) and DLC coatings can both be applied as a single layer or plurallayers of an interior tube or syringe barrel coating.

Referring to FIG. 2, the barrier or other type of coating 90 reduces thetransmission of atmospheric gases into the vessel 80 through itsinterior surface 88. Or, the barrier or other type of coating 90 reducesthe contact of the contents of the vessel 80 with the interior surface88. The barrier or other type of coating can comprise, for example,SiO_(x), amorphous (for example, diamond-like) carbon, or a combinationof these.

Any coating described herein can be used for coating a surface, forexample a plastic surface. It can further be used as a barrier layer,for example as a barrier against a gas or liquid, optionally againstwater vapor, oxygen and/or air. It can also be used for preventing orreducing mechanical and/or chemical effects which the coated surfacewould have on a compound or composition if the surface were uncoated.For example, it can prevent or reduce the precipitation of a compound orcomposition, for example insulin precipitation or blood clotting orplatelet activation.

Evacuated Blood Collection Vessels

Tubes

Referring to FIG. 2, more details of the vessel such as 80 are shown.The illustrated vessel 80 can be generally tubular, having an opening 82at one end of the vessel, opposed by a closed end 84. The vessel 80 alsohas a wall 86 defining an interior surface 88. One example of the vessel80 is a medical sample tube, such as an evacuated blood collection tube,as commonly is used by a phlebotomist for receiving a venipuncturesample of a patient's blood for use in a medical laboratory.

The vessel 80 can be made, for example, of thermoplastic material. Someexamples of suitable thermoplastic material are polyethyleneterephthalate or a polyolefin such as polypropylene or a cyclicpolyolefin copolymer.

The vessel 80 can be made by any suitable method, such as by injectionmolding, by blow molding, by machining, by fabrication from tubingstock, or by other suitable means. PECVD can be used to form a coatingon the internal surface of SiO_(x).

If intended for use as an evacuated blood collection tube, the vessel 80desirably can be strong enough to withstand a substantially totalinternal vacuum substantially without deformation when exposed to anexternal pressure of 760 Torr or atmospheric pressure and other coatingprocessing conditions. This property can be provided, in a thermoplasticvessel 80, by providing a vessel 80 made of suitable materials havingsuitable dimensions and a glass transition temperature higher than theprocessing temperature of the coating process, for example a cylindricalwall 86 having sufficient wall thickness for its diameter and material.

Medical vessels or containers like sample collection tubes and syringesare relatively small and are injection molded with relatively thickwalls, which renders them able to be evacuated without being crushed bythe ambient atmospheric pressure. They are thus stronger than carbonatedsoft drink bottles or other larger or thinner-walled plastic containers.Since sample collection tubes designed for use as evacuated vesselstypically are constructed to withstand a full vacuum during storage,they can be used as vacuum chambers.

Such adaptation of the vessels to be their own vacuum chambers mighteliminate the need to place the vessels into a vacuum chamber for PECVDtreatment, which typically is carried out at very low pressure. The useof a vessel as its own vacuum chamber can result in faster processingtime (since loading and unloading of the parts from a separate vacuumchamber is not necessary) and can lead to simplified equipmentconfigurations. Furthermore, a vessel holder is contemplated, forcertain embodiments, that will hold the device (for alignment to gastubes and other apparatus), seal the device (so that the vacuum can becreated by attaching the vessel holder to a vacuum pump) and move thedevice between molding and subsequent processing steps.

A vessel 80 used as an evacuated blood collection tube should be able towithstand external atmospheric pressure, while internally evacuated to areduced pressure useful for the intended application, without asubstantial volume of air or other atmospheric gas leaking into the tube(as by bypassing the closure) or permeating through the wall 86 duringits shelf life. If the as-molded vessel 80 cannot meet this requirement,it can be processed by coating the interior surface 88 with a barrier orother type of coating 90. It is desirable to treat and/or coat theinterior surfaces of these devices (such as sample collection tubes andsyringe barrels) to impart various properties that will offer advantagesover existing polymeric devices and/or to mimic existing glass products.It is also desirable to measure various properties of the devices beforeand/or after treatment or coating.

Coating Deposited from an Organosilicon Precursor

Made by In Situ Polymerizing Organosilicon Precursor

A process is contemplated for applying a lubricity layer characterizedas defined in the Definition Section on a substrate, for example theinterior of the barrel of a syringe, comprising applying one of thedescribed precursors on or in the vicinity of a substrate at a thicknessof 1 to 5000 nm, optionally 10 to 1000 nm, optionally 10-200 nm,optionally 20 to 100 nm thick and crosslinking or polymerizing (or both)the coating, optionally in a PECVD process, to provide a lubricatedsurface. The coating applied by this process is also contemplated to benew.

A coating of Si_(w)O_(x)C_(y)H_(z) as defined in the Definition Sectionoptionally can be very thin, having a thickness of at least 4 nm, or atleast 7 nm, or at least 10 nm, or at least 20 nm, or at least 30 nm, orat least 40 nm, or at least 50 nm, or at least 100 nm, or at least 150nm, or at least 200 nm, or at least 300 nm, or at least 400 nm, or atleast 500 nm, or at least 600 nm, or at least 700 nm, or at least 800nm, or at least 900 nm. The coating can be up to 1000 nm, or at most 900nm, or at most 800 nm, or at most 700 nm, or at most 600 nm, or at most500 nm, or at most 400 nm, or at most 300 nm, or at most 200 nm, or atmost 100 nm, or at most 90 nm, or at most 80 nm, or at most 70 nm, or atmost 60 nm, or at most 50 nm, or at most 40 nm, or at most 30 nm, or atmost 20 nm, or at most 10 nm, or at most 5 nm thick. Specific thicknessranges composed of any one of the minimum thicknesses expressed above,plus any equal or greater one of the maximum thicknesses expressedabove, are expressly contemplated.

Combinations of acid or base catalysis and heating, using an alkyltrimethoxysilane precursor as described above, can condense theprecursor (removing ROH by-products) to form crosslinked polymers, whichcan optionally be further crosslinked via an alternative method. Onespecific example is by Shimojima et. al. J. Mater. Chem., 2007, 17,658-663.

A lubricity layer, characterized as defined in the Definition Section,can be applied as a subsequent coating after applying an SiO_(x) barrierlayer to the interior surface 88 of the vessel 80 to provide a lubricitylayer, particularly if the lubricity layer is a liquid organosiloxanecompound at the end of the coating process.

Optionally, after the lubricity layer is applied, it can be post-curedafter the PECVD process. Radiation curing approaches, includingUV-initiated (free radial or cationic), electron-beam (E-beam), andthermal as described in Development Of Novel Cycloaliphatic SiloxanesFor Thermal And UV-Curable Applications (Ruby Chakraborty Dissertation,can 2008) be utilized.

Another approach for providing a lubricity layer is to use a siliconedemolding agent when injection-molding the thermoplastic vessel to belubricated. For example, it is contemplated that any of the demoldingagents and latent monomers causing in-situ thermal lubricity layerformation during the molding process can be used. Or, the aforementionedmonomers can be doped into traditional demolding agents to accomplishthe same result.

A lubricity layer, characterized as defined in the Definition Section,is particularly contemplated for the internal surface of a syringebarrel as further described below. A lubricated internal surface of asyringe barrel can reduce the plunger sliding force needed to advance aplunger in the barrel during operation of a syringe, or the breakoutforce to start a plunger moving after the prefilled syringe plunger haspushed away the intervening lubricant or adhered to the barrel, forexample due to decomposition of the lubricant between the plunger andthe barrel. As explained elsewhere in this specification, a lubricitylayer also can be applied to the interior surface 88 of the vessel 80 toimprove adhesion of a subsequent coating of SiO_(x).

Thus, the coating 90 can comprise a layer of SiO_(x) and a lubricitylayer, characterized as defined in the Definition Section. The lubricitylayer of Si_(w)O_(x)C_(y)H_(z) can be deposited between the layer ofSiO_(x) and the interior surface of the vessel. Or, the layer of SiO_(x)can be deposited between the lubricity layer and the interior surface ofthe vessel. Or, three or more layers, either alternating or graduatedbetween these two coating compositions: (1) a layer of SiO_(x) and (2)the lubricity layer; can also be used. The layer of SiO_(x) can bedeposited adjacent to the lubricity layer or remotely, with at least oneintervening layer of another material. The layer of SiO_(x) can bedeposited adjacent to the interior surface of the vessel. Or, thelubricity layer can be deposited adjacent to the interior surface of thevessel.

Another expedient contemplated here, for adjacent layers of SiO_(x) anda lubricity layer, is a graded composite of Si_(w)O_(x)C_(y)H_(z), asdefined in the Definition Section. A graded composite can be separatelayers of a lubricity layer and SiO_(x) with a transition or interfaceof intermediate composition between them, or separate layers of alubricity layer and SiOx with an intermediate distinct layer ofintermediate composition between them, or a single layer that changescontinuously or in steps from a composition of a lubricity layer to acomposition more like SiO_(x), going through the coating in a normaldirection.

The grade in the graded composite can go in either direction. Forexample, the lubricity layer can be applied directly to the substrateand graduate to a composition further from the surface of SiO_(x). Or,the composition of SiO_(x) can be applied directly to the substrate andgraduate to a composition further from the surface of a lubricity layer.A graduated coating is particularly contemplated if a coating of onecomposition is better for adhering to the substrate than the other, inwhich case the better-adhering composition can, for example, be applieddirectly to the substrate. It is contemplated that the more distantportions of the graded coating can be less compatible with the substratethan the adjacent portions of the graded coating, since at any point thecoating is changing gradually in properties, so adjacent portions atnearly the same depth of the coating have nearly identical composition,and more widely physically separated portions at substantially differentdepths can have more diverse properties. It is also contemplated that acoating portion that forms a better barrier against transfer of materialto or from the substrate can be directly against the substrate, toprevent the more remote coating portion that forms a poorer barrier frombeing contaminated with the material intended to be barred or impeded bythe barrier.

The coating, instead of being graded, optionally can have sharptransitions between one layer and the next, without a substantialgradient of composition. Such coatings can be made, for example, byproviding the gases to produce a layer as a steady state flow in anon-plasma state, then energizing the system with a brief plasmadischarge to form a coating on the substrate. If a subsequent coating isto be applied, the gases for the previous coating are cleared out andthe gases for the next coating are applied in a steady-state fashionbefore energizing the plasma and again forming a distinct layer on thesurface of the substrate or its outermost previous coating, with littleif any gradual transition at the interface.

SiO_(x) Barrier Coated Double Wall Plastic Vessel—COC, PET, SiO_(x)Layers

Another embodiment is a vessel having a wall at least partiallyenclosing a lumen. The wall has an interior polymer layer enclosed by anexterior polymer layer. One of the polymer layers is a layer at least0.1 mm thick of a cyclic olefin copolymer (COC) resin defining a watervapor barrier. Another of the polymer layers is a layer at least 0.1 mmthick of a polyester resin.

The wall includes an oxygen barrier layer of SiO_(x) having a thicknessof from about 10 to about 500 angstroms.

In an embodiment, illustrated in FIG. 11, the vessel 80 can be adouble-walled vessel having an inner wall 408 and an outer wall 410,respectively made of the same or different materials. One particularembodiment of this type can be made with one wall molded from a cyclicolefin copolymer (COC) and the other wall molded from a polyester suchas polyethylene terephthalate (PET), with an SiO_(x) coating aspreviously described on the interior surface 412. As needed, a tiecoating or layer can be inserted between the inner and outer walls topromote adhesion between them. An advantage of this wall construction isthat walls having different properties can be combined to form acomposite having the respective properties of each wall.

As one example, the inner wall 408 can be made of PET coated on theinterior surface 412 with an SiO_(x) barrier layer, and the outer wall410 can be made of COC. PET coated with SiO_(x), as shown elsewhere inthis specification, is an excellent oxygen barrier, while COC is anexcellent barrier for water vapor, providing a low water vaportransition rate (WVTR). This composite vessel can have superior barrierproperties for both oxygen and water vapor. This construction iscontemplated, for example, for an evacuated medical sample collectiontube that contains an aqueous reagent as manufactured, and has asubstantial shelf life, so it should have a barrier preventing transferof water vapor outward or transfer of oxygen or other gases inwardthrough its composite wall during its shelf life.

As another example, the inner wall 408 can be made of COC coated on theinterior surface 412 with an SiO_(x) barrier layer, and the outer wall410 can be made of PET. This construction is contemplated, for example,for a prefilled syringe that contains an aqueous sterile fluid asmanufactured. The SiO_(x) barrier will prevent oxygen from entering thesyringe through its wall. The COC inner wall will prevent ingress oregress of other materials such as water, thus preventing the water inthe aqueous sterile fluid from leaching materials from the wall materialinto the syringe. The COC inner wall is also contemplated to preventwater derived from the aqueous sterile fluid from passing out of thesyringe (thus undesirably concentrating the aqueous sterile fluid), andwill prevent non-sterile water or other fluids outside the syringe fromentering through the syringe wall and causing the contents to becomenon-sterile. The COC inner wall is also contemplated to be useful fordecreasing the breaking force or friction of the plunger against theinner wall of a syringe.

Method of Making Double Wall Plastic Vessel—COC, PET, SiO_(x) Layers

Another embodiment is a method of making a vessel having a wall havingan interior polymer layer enclosed by an exterior polymer layer, onelayer made of COC and the other made of polyester. The vessel is made bya process including introducing COC and polyester resin layers into aninjection mold through concentric injection nozzles.

An optional additional step is applying an amorphous carbon coating tothe vessel by PECVD, as an inside coating, an outside coating, or as aninterlayer coating located between the layers.

An optional additional step is applying an SiO_(x) barrier layer to theinside of the vessel wall, where SiO_(x) is defined as before. Anotheroptional additional step is post-treating the SiO_(x) layer with aprocess gas consisting essentially of oxygen and essentially free of avolatile silicon compound.

Optionally, the SiO_(x) coating can be formed at least partially from asilazane feed gas.

The vessel 80 shown in FIG. 11 can be made from the inside out, for oneexample, by injection molding the inner wall in a first mold cavity,then removing the core and molded inner wall from the first mold cavityto a second, larger mold cavity, then injection molding the outer wallagainst the inner wall in the second mold cavity. Optionally, a tielayer can be provided to the exterior surface of the molded inner wallbefore over-molding the outer wall onto the tie layer.

Or, the vessel 80 shown in FIG. 11 can be made from the outside in, forone example, by inserting a first core in the mold cavity, injectionmolding the outer wall in the mold cavity, then removing the first corefrom the molded first wall and inserting a second, smaller core, theninjection molding the inner wall against the outer wall still residingin the mold cavity. Optionally, a tie layer can be provided to theinterior surface of the molded outer wall before over-molding the innerwall onto the tie layer.

Or, the vessel 80 shown in FIG. 11 can be made in a two shot mold. Thiscan be done, for one example, by injection molding material for theinner wall from an inner nozzle and the material for the outer wall froma concentric outer nozzle. Optionally, a tie layer can be provided froma third, concentric nozzle disposed between the inner and outer nozzles.The nozzles can feed the respective wall materials simultaneously. Oneuseful expedient is to begin feeding the outer wall material through theouter nozzle slightly before feeding the inner wall material through theinner nozzle. If there is an intermediate concentric nozzle, the orderof flow can begin with the outer nozzle and continue in sequence fromthe intermediate nozzle and then from the inner nozzle. Or, the order ofbeginning feeding can start from the inside nozzle and work outward, inreverse order compared to the preceding description.

Barrier Layer Made of Glass

Another embodiment is a vessel including a barrier layer and a closure.The vessel is generally tubular and made of thermoplastic material. Thevessel has a mouth and a lumen bounded at least in part by a wall havingan inner surface interfacing with the lumen. There is an at leastessentially continuous barrier layer made of glass on the inner surfaceof the wall. A closure covers the mouth and isolates the lumen of thevessel from ambient air.

The vessel 80 can also be made, for example of glass of any type used inmedical or laboratory applications, such as soda-lime glass,borosilicate glass, or other glass formulations. Other vessels havingany shape or size, made of any material, are also contemplated for usein the system 20. One function of coating a glass vessel can be toreduce the ingress of ions in the glass, either intentionally or asimpurities, for example sodium, calcium, or others, from the glass tothe contents of the vessel, such as a reagent or blood in an evacuatedblood collection tube. Another function of coating a glass vessel inwhole or in part, such as selectively at surfaces contacted in slidingrelation to other parts, is to provide lubricity to the coating, forexample to ease the insertion or removal of a stopper or passage of asliding element such as a piston in a syringe. Still another reason tocoat a glass vessel is to prevent a reagent or intended sample for thevessel, such as blood, from sticking to the wall of the vessel or anincrease in the rate of coagulation of the blood in contact with thewall of the vessel.

A related embodiment is a vessel as described in the previous paragraph,in which the barrier layer is made of soda lime glass, borosilicateglass, or another type of glass.

Stoppers

FIGS. 7-9 illustrate a vessel 268, which can be an evacuated bloodcollection tube, having a closure 270 to isolate the lumen 274 from theambient environment. The closure 270 comprises a interior-facing surface272 exposed to the lumen 274 of the vessel 268 and a wall-contactingsurface 276 that is in contact with the inner surface 278 of the vesselwall 280. In the illustrated embodiment the closure 270 is an assemblyof a stopper 282 and a shield 284.

Method of Applying Lubricity Layer to Stopper in Vacuum Chamber

Another embodiment is a method of applying a coating on an elastomericstopper such as 282. The stopper 282, separate from the vessel 268, isplaced in a substantially evacuated chamber. A reaction mixture isprovided including plasma forming gas, i.e. an organosilicon compoundgas, optionally an oxidizing gas, and optionally a hydrocarbon gas.Plasma is formed in the reaction mixture, which is contacted with thestopper. A lubricity, characterized as defined in the DefinitionSection, is deposited on at least a portion of the stopper.

In the illustrated embodiment, the wall-contacting surface 276 of theclosure 270 is coated with a lubricity layer 286.

In some embodiments, the lubricity layer, characterized as defined inthe Definition Section, is effective to reduce the transmission of oneor more constituents of the stopper, such as a metal ion constituent ofthe stopper, or of the vessel wall, into the vessel lumen. Certainelastomeric compositions of the type useful for fabricating a stopper282 contain trace amounts of one or more metal ions. These ionssometimes should not be able to migrate into the lumen 274 or come insubstantial quantities into contact with the vessel contents,particularly if the sample vessel 268 is to be used to collect a samplefor trace metal analysis. It is contemplated for example that coatingscontaining relatively little organic content, i.e. where y and z ofSi_(w)O_(x)C_(y)H_(z) as defined in the Definition Section are low orzero, are particularly useful as a metal ion barrier in thisapplication. Regarding silica as a metal ion barrier see, for example,Anupama Mallikarjunan, Jasbir Juneja, Guangrong Yang, Shyam P. Murarka,and Toh-Ming Lu, The Effect of Interfacial Chemistry on Metal IonPenetration into Polymeric Films, Mat. Res. Soc. Symp. Proc., Vol. 734,pp. B9.60.1 to B9.60.6 (Materials Research Society, 2003); U.S. Pat.Nos. 5,578,103 and 6,200,658, and European Appl. EP0697378 A2, which areall incorporated here by reference. It is contemplated, however, thatsome organic content can be useful to provide a more elastic coating andto adhere the coating to the elastomeric surface of the stopper 282.

In some embodiments, the lubricity layer, characterized as defined inthe Definition Section, can be a composite of material having first andsecond layers, in which the first or inner layer 288 interfaces with theelastomeric stopper 282 and is effective to reduce the transmission ofone or more constituents of the stopper 282 into the vessel lumen. Thesecond layer 286 can interface with the inner wall 280 of the vessel andis effective as a lubricity layer to reduce friction between the stopper282 and the inner wall 280 of the vessel when the stopper 282 is seatedon or in the vessel 268. Such composites are described in connectionwith syringe coatings elsewhere in this specification.

Or, the first and second layers 288 and 286 are defined by a coating ofgraduated properties, in which the values of y and z defined in theDefinition Section are greater in the first layer than in the secondlayer.

The lubricity layer can be applied, for example, by PECVD substantiallyas previously described. The lubricity can be, for example, between 0.5and 5000 nm (5 to 50,000 Angstroms) thick, or between 1 and 5000 nmthick, or between 5 and 5000 nm thick, or between 10 and 5000 nm thick,or between 20 and 5000 nm thick, or between 50 and 5000 nm thick, orbetween 100 and 5000 nm thick, or between 200 and 5000 nm thick, orbetween 500 and 5000 nm thick, or between 1000 and 5000 nm thick, orbetween 2000 and 5000 nm thick, or between 3000 and 5000 nm thick, orbetween 4000 and 10,000 nm thick.

Certain advantages are contemplated for plasma coated lubricity layers,versus the much thicker (one micron or greater) conventional sprayapplied silicone lubricants. Plasma coatings have a much lower migratorypotential to move into blood versus sprayed or micron-coated silicones,both because the amount of plasma coated material is much less andbecause it can be more intimately applied to the coated surface andbetter bonded in place.

Nanocoatings, as applied by PECVD, are contemplated to offer lowerresistance to sliding of an adjacent surface or flow of an adjacentfluid than micron coatings, as the plasma coating tends to provide asmoother surface.

Still another embodiment is a method of applying a coating of alubricity on an elastomeric stopper. The stopper can be used, forexample, to close the vessel previously described. The method includesseveral parts. A stopper is placed in a substantially evacuated chamber.A reaction mixture is provided comprising plasma forming gas, i.e. anorganosilicon compound gas, optionally an oxidizing gas, and optionallya hydrocarbon gas. Plasma is formed in the reaction mixture. The stopperis contacted with the reaction mixture, depositing the coating of alubricity on at least a portion of the stopper.

In practicing this method, to obtain higher values of y and z as definedin the Definition Section, it is contemplated that the reaction mixturecan comprise a hydrocarbon gas, as further described above and below.Optionally, the reaction mixture can contain oxygen, if lower values ofy and z or higher values of x are contemplated. Or, particularly toreduce oxidation and increase the values of y and z, the reactionmixture can be essentially free of an oxidizing gas.

In practicing this method to coat certain embodiments of the stoppersuch as the stopper 282, it is contemplated to be unnecessary to projectthe reaction mixture into the concavities of the stopper. For example,the wall-contacting and interior facing surfaces 276 and 272 of thestopper 282 are essentially convex, and thus readily treated by a batchprocess in which a multiplicity of stoppers such as 282 can be locatedand treated in a single substantially evacuated reaction chamber. It isfurther contemplated that in some embodiments the coatings 286 and 288do not need to present as formidable a barrier to oxygen or water as thebarrier layer on the interior surface 280 of the vessel 268, as thematerial of the stopper 282 can serve this function to a large degree.

Many variations of the stopper and the stopper coating process arecontemplated. The stopper 282 can be contacted with the plasma. Or, theplasma can be formed upstream of the stopper 282, producing plasmaproduct, and the plasma product can be contacted with the stopper 282.The plasma can be formed by exciting the reaction mixture withelectromagnetic energy and/or microwave energy.

Variations of the reaction mixture are contemplated. The plasma forminggas can include an inert gas. The inert gas can be, for example, argonor helium, or other gases described in this disclosure. Theorganosilicon compound gas can be, or include, HMDSO, OMCTS, any of theother organosilicon compounds mentioned in this disclosure, or acombination of two or more of these. The oxidizing gas can be oxygen orthe other gases mentioned in this disclosure, or a combination of two ormore of these. The hydrocarbon gas can be, for example, methane,methanol, ethane, ethylene, ethanol, propane, propylene, propanol,acetylene, or a combination of two or more of these.

Applying by PECVD a Coating of Group III or IV Element and Carbon on aStopper

Another embodiment is a method of applying a coating of a compositionincluding carbon and one or more elements of Groups III or IV on anelastomeric stopper. To carry out the method, a stopper is located in adeposition chamber.

A reaction mixture is provided in the deposition chamber, including aplasma forming gas with a gaseous source of a Group III element, a GroupIV element, or a combination of two or more of these. The reactionmixture optionally contains an oxidizing gas and optionally contains agaseous compound having one or more C—H bonds. Plasma is formed in thereaction mixture, and the stopper is contacted with the reactionmixture. A coating of a Group III element or compound, a Group IVelement or compound, or a combination of two or more of these isdeposited on at least a portion of the stopper.

Stoppered Plastic Vessel Having Barrier Layer Effective to Provide 95%Vacuum Retention for 24 Months

Another embodiment is a vessel including a barrier layer and a closure.The vessel is generally tubular and made of thermoplastic material. Thevessel has a mouth and a lumen bounded at least in part by a wall. Thewall has an inner surface interfacing with the lumen. An at leastessentially continuous barrier layer is applied on the inner surface ofthe wall. The barrier layer is effective to provide a substantial shelflife. A closure is provided covering the mouth of the vessel andisolating the lumen of the vessel from ambient air.

Referring to FIGS. 7-9, a vessel 268 such as an evacuated bloodcollection tube or other vessel is shown.

The vessel is, in this embodiment, a generally tubular vessel having anat least essentially continuous barrier layer and a closure. The vesselis made of thermoplastic material having a mouth and a lumen bounded atleast in part by a wall having an inner surface interfacing with thelumen. The barrier layer is deposited on the inner surface of the wall,and is effective to maintain at least 95%, or at least 90%, of theinitial vacuum level of the vessel for a shelf life of at least 24months, optionally at least 30 months, optionally at least 36 months.The closure covers the mouth of the vessel and isolates the lumen of thevessel from ambient air.

The closure, for example the closure 270 illustrated in the Figures oranother type of closure, is provided to maintain a partial vacuum and/orto contain a sample and limit or prevent its exposure to oxygen orcontaminants. FIGS. 7-9 are based on figures found in U.S. Pat. No.6,602,206, but the present discovery is not limited to that or any otherparticular type of closure.

The closure 270 comprises a interior-facing surface 272 exposed to thelumen 274 of the vessel 268 and a wall-contacting surface 276 that is incontact with the inner surface 278 of the vessel wall 280. In theillustrated embodiment the closure 270 is an assembly of a stopper 282and a shield 284.

In the illustrated embodiment, the stopper 282 defines thewall-contacting surface 276 and the inner surface 278, while the shieldis largely or entirely outside the stoppered vessel 268, retains andprovides a grip for the stopper 282, and shields a person removing theclosure 270 from being exposed to any contents expelled from the vessel268, such as due to a pressure difference inside and outside of thevessel 268 when the vessel 268 is opened and air rushes in or out toequalize the pressure difference.

It is further contemplated that the coatings on the vessel wall 280 andthe wall contacting surface 276 of the stopper can be coordinated. Thestopper can be coated with a lubricity silicone layer, and the vesselwall 280, made for example of PET or glass, can be coated with a harderSiO_(x) layer, or with an underlying SiOx layer and a lubricityovercoat.

Syringes

The foregoing description has largely addressed applying a barrier layerto a tube with one permanently closed end, such as a blood collectiontube or, more generally, a specimen receiving tube 80. The apparatus isnot limited to such a device.

Another example of a suitable vessel, shown in FIGS. 5-6, is a syringebarrel 250 for a medical syringe 252. Such syringes 252 are sometimessupplied prefilled with saline solution, a pharmaceutical preparation,or the like for use in medical techniques. Pre-filled syringes 252 arealso contemplated to benefit from an SiO_(x) barrier or other type ofcoating on the interior surface 254 to keep the contents of theprefilled syringe 252 out of contact with the plastic of the syringe,for example of the syringe barrel 250 during storage. The barrier orother type of coating can be used to avoid leaching components of theplastic into the contents of the barrel through the interior surface254.

A syringe barrel 250 as molded commonly can be open at both the back end256, to receive a plunger 258, and at the front end 260, to receive ahypodermic needle, a nozzle, or tubing for dispensing the contents ofthe syringe 252 or for receiving material into the syringe 252. But thefront end 260 can optionally be capped and the plunger 258 optionallycan be fitted in place before the prefilled syringe 252 is used, closingthe barrel 250 at both ends. A cap 262 can be installed either for thepurpose of processing the syringe barrel 250 or assembled syringe, or toremain in place during storage of the prefilled syringe 252, up to thetime the cap 262 is removed and (optionally) a hypodermic needle orother delivery conduit is fitted on the front end 260 to prepare thesyringe 252 for use.

Assemblies

FIG. 5 also shows an alternative syringe barrel construction.

FIG. 5 is an exploded view of a syringe. The syringe barrel can beprocessed with the vessel treatment and inspection apparatus of FIGS.1-6 and 15-16.

The installation of a cap 262 makes the barrel 250 a closed-end vesselthat can be provided with an SiO_(x) barrier or other type of coating onits interior surface 254 in the previously illustrated apparatus,optionally also providing a coating on the interior 264 of the cap andbridging the interface between the cap interior 264 and the barrel frontend 260. Suitable apparatus adapted for this use is shown, for example,in FIG. 6, which is analogous to FIG. 2 except for the substitution ofthe capped syringe barrel 250 for the vessel 80 of FIG. 2.

Syringe Having Barrel Coated with Lubricity Layer Deposited from anOrganosilicon Precursor

Still another embodiment is a vessel having a lubricity layer,characterized as defined in the Definition Section, of the type made bythe following process.

A precursor is provided as defined above.

The precursor is applied to a substrate under conditions effective toform a coating. The coating is polymerized or crosslinked, or both, toform a lubricated surface having a lower plunger sliding force orbreakout force than the untreated substrate.

Optionally, the applying step is carried out by vaporizing the precursorand providing it in the vicinity of the substrate.

Respecting any of the Embodiments i, optionally a plasma, optionally anon-hollow-cathode plasma, is formed in the vicinity of the substrate.Optionally, the precursor is provided in the substantial absence ofoxygen. Optionally, the precursor is provided in the substantial absenceof a carrier gas. Optionally, the precursor is provided in thesubstantial absence of nitrogen. Optionally, the precursor is providedat less than 1 Torr absolute pressure. Optionally, the precursor isprovided to the vicinity of a plasma emission. Optionally, the precursorits reaction product is applied to the substrate at a thickness of 1 to5000 nm thick, or 10 to 1000 nm thick, or 10-200 nm thick, or 20 to 100nm thick. Optionally, the substrate comprises glass. Optionally, thesubstrate comprises a polymer, optionally a polycarbonate polymer,optionally an olefin polymer, optionally a cyclic olefin copolymer,optionally a polypropylene polymer, optionally a polyester polymer,optionally a polyethylene terephthalate polymer.

Optionally, the plasma is generated by energizing the gaseous reactantcontaining the precursor with electrodes powered, for example, at a RFfrequency as defined above, for example a frequency of from 10 kHz toless than 300 MHz, optionally from 1 to 50 MHz, even optionally from 10to 15 MHz, optionally a frequency of 13.56 MHz.

Optionally, the plasma is generated by energizing the gaseous reactantcontaining the precursor with electrodes supplied with an electric powerof from 0.1 to 25 W, optionally from 1 to 22 W, optionally from 3 to 17W, even optionally from 5 to 14 W, optionally from 7 to 11 W, optionally8 W. The ratio of the electrode power to the plasma volume can be lessthan 10 W/ml, optionally is from 5 W/ml to 0.1 W/ml, optionally is from4 W/ml to 0.1 W/ml, optionally from 2 W/ml to 0.2 W/ml. These powerlevels are suitable for applying lubricity layers to syringes and sampletubes and vessels of similar geometry having a void volume of 1 to 3 mLin which PECVD plasma is generated. It is contemplated that for largeror smaller objects the power applied should be increased or reducedaccordingly to scale the process to the size of the substrate.

Another embodiment is a lubricity layer, characterized as defined in theDefinition Section, on the inner wall of a syringe barrel. The coatingis produced from a PECVD process using the following materials andconditions. A cyclic precursor is optionally employed, selected from amonocyclic siloxane, a polycyclic siloxane, or a combination of two ormore of these, as defined elsewhere in this specification for lubricitylayers. One example of a suitable cyclic precursor comprisesoctamethylcyclotetrasiloxane (OMCTS), optionally mixed with otherprecursor materials in any proportion. Optionally, the cyclic precursorconsists essentially of octamethylcyclotetrasiloxane (OMCTS), meaningthat other precursors can be present in amounts which do not change thebasic and novel properties of the resulting lubricity layer, i.e. itsreduction of the plunger sliding force or breakout force of the coatedsurface.

Optionally, at least essentially no oxygen, as defined in the DefinitionSection is added to the process.

A sufficient plasma generation power input, for example any power levelsuccessfully used in one or more working examples of this specificationor described in the specification, is provided to induce coatingformation.

The materials and conditions employed are effective to reduce thesyringe plunger sliding force or breakout force moving through thesyringe barrel at least 25 percent, alternatively at least 45 percent,alternatively at least 60 percent, alternatively greater than 60percent, relative to an uncoated syringe barrel. Ranges of plungersliding force or breakout force reduction of from 20 to 95 percent,alternatively from 30 to 80 percent, alternatively from 40 to 75percent, alternatively from 60 to 70 percent, are contemplated.

Respecting any of the embodiments, optionally the substrate comprisesglass or a polymer. The glass optionally is borosilicate glass. Thepolymer is optionally a polycarbonate polymer, optionally an olefinpolymer, optionally a cyclic olefin copolymer, optionally apolypropylene polymer, optionally a polyester polymer, optionally apolyethylene terephthalate polymer.

Another embodiment is a syringe including a plunger, a syringe barrel,and a lubricity layer, characterized as defined in the DefinitionSection. The syringe barrel includes an interior surface receiving theplunger for sliding. The lubricity layer is disposed on the interiorsurface of the syringe barrel. The lubricity layer is less than 1000 nmthick and effective to reduce the breakout force or the plunger slidingforce necessary to move the plunger within the barrel. Reducing theplunger sliding force is alternatively expressed as reducing thecoefficient of sliding friction of the plunger within the barrel orreducing the plunger force; these terms are regarded as having the samemeaning in this specification.

Any of the above precursors of any type can be used alone or incombinations of two or more of them to provide a lubricity layer.

In addition to utilizing vacuum processes, low temperature atmospheric(non-vacuum) plasma processes can also be utilized to induce molecularionization and deposition through precursor monomer vapor deliveryoptionally in a non-oxidizing atmosphere such as helium or argon.Separately, thermal CVD can be considered via flash thermolysisdeposition.

The approaches above are similar to vacuum PECVD in that the surfacecoating and crosslinking mechanisms can occur simultaneously.

Yet another expedient contemplated for any coating or coatings describedhere is a coating that is not uniformly applied over the entire interior88 of a vessel. For example, a different or additional coating can beapplied selectively to the cylindrical portion of the vessel interior,compared to the hemispherical portion of the vessel interior at itsclosed end 84, or vice versa. This expedient is particularlycontemplated for a syringe barrel or a sample collection tube asdescribed below, in which a lubricity layer might be provided on part orall of the cylindrical portion of the barrel, where the plunger orpiston or closure slides, and not elsewhere.

Optionally, the precursor can be provided in the presence, substantialabsence, or absence of oxygen, in the presence, substantial absence, orabsence of nitrogen, or in the presence, substantial absence, or absenceof a carrier gas. In one contemplated embodiment, the precursor alone isdelivered to the substrate and subjected to PECVD to apply and cure thecoating.

Optionally, the precursor can be provided at less than 1 Torr absolutepressure.

Optionally, the precursor can be provided to the vicinity of a plasmaemission.

Optionally, the precursor or its reaction product can be applied to thesubstrate at a thickness of 1 to 5000 nm, or 10 to 1000 nm, or 10-200nm, or 20 to 100 nm.

In any of the above embodiments, the substrate can comprise glass, or apolymer, for example one or more of a polycarbonate polymer, an olefinpolymer (for example a cyclic olefin copolymer or a polypropylenepolymer), or a polyester polymer (for example, a polyethyleneterephthalate polymer).

In any of the above embodiments, the plasma is generated by energizingthe gaseous reactant containing the precursor with electrodes powered ata RF frequency as defined in this description.

In any of the above embodiments, the plasma is generated by energizingthe gaseous reactant containing the precursor with electrodes suppliedwith sufficient electric power to generate a lubricity layer.Optionally, the plasma is generated by energizing the gaseous reactantcontaining the precursor with electrodes supplied with an electric powerof from 0.1 to 25 W, optionally from 1 to 22 W, optionally from 3 to 17W, even optionally from 5 to 14 W, optionally from 7 to 11 W, optionally8 W. The ratio of the electrode power to the plasma volume can be lessthan 10 W/ml, optionally is from 5 W/ml to 0.1 W/ml, optionally is from4 W/ml to 0.1 W/ml, optionally from 2 W/ml to 0.2 W/ml. These powerlevels are suitable for applying lubricity layers to syringes and sampletubes and vessels of similar geometry having a void volume of 1 to 3 mLin which PECVD plasma is generated. It is contemplated that for largeror smaller objects the power applied should be increased or reducedaccordingly to scale the process to the size of the substrate.

The coating can be cured, as by polymerizing or crosslinking thecoating, or both, to form a lubricated surface having a lower plungersliding force or breakout force than the untreated substrate. Curing canoccur during the application process such as PECVD, or can be carriedout or at least completed by separate processing.

Although plasma deposition has been used herein to demonstrate thecoating characteristics, alternate deposition methods can be used aslong as the chemical composition of the starting material is preservedas much as possible while still depositing a solid film that is adheredto the base substrate.

For example, the coating material can be applied onto the syringe barrel(from the liquid state) by spraying the coating or dipping the substrateinto the coating, where the coating is either the neat precursor asolvent-diluted precursor (allowing the mechanical deposition of athinner coating). The coating optionally can be crosslinked usingthermal energy, UV energy, electron beam energy, plasma energy, or anycombination of these.

Application of a silicone precursor as described above onto a surfacefollowed by a separate curing step is also contemplated. The conditionsof application and curing can be analogous to those used for theatmospheric plasma curing of pre-coated polyfluoroalkyl ethers, aprocess practiced under the trademark TriboGlide®. More details of thisprocess can be found at http://www.triboglide.com/process.htm.

In such a process, the area of the part to be coated can optionally bepre-treated with an atmospheric plasma. This pretreatment cleans andactivates the surface so that it is receptive to the lubricant that issprayed in the next step.

The lubrication fluid, in this case one of the above precursors or apolymerized precursor, is then sprayed on to the surface to be treated.For example, IVEK precision dispensing technology can be used toaccurately atomize the fluid and create a uniform coating.

The coating is then bonded or crosslinked to the part, again using anatmospheric plasma field. This both immobilizes the coating and improvesthe lubricant's performance.

Optionally, the atmospheric plasma can be generated from ambient air inthe vessel, in which case no gas feed and no vacuum drawing equipment isneeded. Optionally, however, the vessel is at least substantially closedwhile plasma is generated, to minimize the power requirement and preventcontact of the plasma with surfaces or materials outside the vessel.

Lubricity Layer: SiO_(x) Barrier, Lubricity Layer, Surface Treatment

Surface Treatment

Another embodiment is a syringe comprising a barrel defining a lumen andhaving an interior surface slidably receiving a plunger, i.e. receivinga plunger for sliding contact to the interior surface.

The syringe barrel is made of thermoplastic base material.

Optionally, the interior surface of the barrel is coated with an SiO_(x)barrier layer as described elsewhere in this specification.

A lubricity layer is applied to the barrel interior surface, theplunger, or both, or to the previously applied SiO_(x) barrier layer.The lubricity layer can be provided, applied, and cured as set out inthis specification.

For example, the lubricity layer can be applied, in any embodiment, byPECVD. The lubricity layer is deposited from an organosilicon precursor,and is less than 1000 nm thick.

A surface treatment is carried out on the lubricity layer in an amounteffective to reduce the leaching or extractables of the lubricity layer,the thermoplastic base material, or both. The treated surface can thusact as a solute retainer. This surface treatment can result in a skincoating, e.g. a skin coating which is at least 1 nm thick and less than100 nm thick, or less than 50 nm thick, or less than 40 nm thick, orless than 30 nm thick, or less than 20 nm thick, or less than 10 nmthick, or less than 5 nm thick, or less than 3 nm thick, or less than 2nm thick, or less than 1 nm thick, or less than 0.5 nm thick.

As used herein, “leaching” refers to material transferred out of asubstrate, such as a vessel wall, into the contents of a vessel, forexample a syringe. Commonly, leachables are measured by storing thevessel filled with intended contents, then analyzing the contents todetermine what material leached from the vessel wall into the intendedcontents. “Extraction” refers to material removed from a substrate byintroducing a solvent or dispersion medium other than the intendedcontents of the vessel, to determine what material can be removed fromthe substrate into the extraction medium under the conditions of thetest.

The surface treatment resulting in a solute retainer optionally can be aSiO_(x) layer as previously defined in this specification, characterizedas defined in the Definition Section. In one embodiment, the surfacetreatment can be applied by PECVD deposit of SiO_(x). Optionally, thesurface treatment can be applied using higher power or strongeroxidation conditions than used for creating the lubricity layer, orboth, thus providing a harder, thinner, continuous solute retainer 539.Surface treatment can be less than 100 nm deep, optionally less than 50nm deep, optionally less than 40 nm deep, optionally less than 30 nmdeep, optionally less than 20 nm deep, optionally less than 10 nm deep,optionally less than 5 nm deep, optionally less than 3 nm deep,optionally less than 1 nm deep, optionally less than 0.5 nm deep,optionally between 0.1 and 50 nm deep in the lubricity layer.

The solute retainer is contemplated to provide low solute leachingperformance to the underlying lubricity and other layers, including thesubstrate, as required. This retainer would only need to be a soluteretainer to large solute molecules and oligomers (for example siloxanemonomers such as HMDSO, OMCTS, their fragments and mobile oligomersderived from lubricants, for example a “leachables retainer”) and not agas (O₂/N₂/CO₂/water vapor) barrier layer. A solute retainer can,however, also be a gas barrier (e.g. the SiO_(x) coating according topresent invention. One can create a good leachable retainer without gasbarrier performance, either by vacuum or atmospheric-based PECVDprocesses. It is desirable that the “leachables barrier” will besufficiently thin that, upon syringe plunger movement, the plunger willreadily penetrate the “solute retainer” exposing the sliding plungernipple to the lubricity layer immediately below to form a lubricatedsurface having a lower plunger sliding force or breakout force than theuntreated substrate.

In another embodiment, the surface treatment can be performed byoxidizing the surface of a previously applied lubricity layer, as byexposing the surface to oxygen in a plasma environment. The plasmaenvironment described in this specification for forming SiO_(x) coatingscan be used. Or, atmospheric plasma conditions can be employed in anoxygen-rich environment.

The lubricity layer and solute retainer, however formed, optionally canbe cured at the same time. In another embodiment, the lubricity layercan be at least partially cured, optionally fully cured, after which thesurface treatment can be provided, applied, and the solute retainer canbe cured.

The lubricity layer and solute retainer are composed, and present inrelative amounts, effective to provide a breakout force, plunger slidingforce, or both that is less than the corresponding force required in theabsence of the lubricity layer and surface treatment. In other words,the thickness and composition of the solute retainer are such as toreduce the leaching of material from the lubricity layer into thecontents of the syringe, while allowing the underlying lubricity layerto lubricate the plunger. It is contemplated that the solute retainerwill break away easily and be thin enough that the lubricity layer willstill function to lubricate the plunger when it is moved.

In one contemplated embodiment, the lubricity and surface treatments canbe applied on the barrel interior surface. In another contemplatedembodiment, the lubricity and surface treatments can be applied on theplunger. In still another contemplated embodiment, the lubricity andsurface treatments can be applied both on the barrel interior surfaceand on the plunger. In any of these embodiments, the optional SiO_(x)barrier layer on the interior of the syringe barrel can either bepresent or absent.

One embodiment contemplated is a plural-layer, e.g. a 3-layer,configuration applied to the inside surface of a syringe barrel. Layer 1can be an SiO_(x) gas barrier made by PECVD of HMDSO, OMCTS, or both, inan oxidizing atmosphere. Such an atmosphere can be provided, forexample, by feeding HMDSO and oxygen gas to a PECVD coating apparatus asdescribed in this specification. Layer 2 can be a lubricity layer usingOMCTS applied in a non-oxidizing atmosphere. Such a non-oxidizingatmosphere can be provided, for example, by feeding OMCTS to a PECVDcoating apparatus as described in this specification, optionally in thesubstantial or complete absence of oxygen. A subsequent solute retainercan be formed by a treatment forming a thin skin layer of SiO_(x) as asolute retainer using higher power and oxygen using OMCTS and/or HMDSO.

Certain of these plural-layer coatings are contemplated to have one ormore of the following optional advantages, at least to some degree. Theycan address the reported difficulty of handling silicone, since thesolute retainer can confine the interior silicone and prevent it frommigrating into the contents of the syringe or elsewhere, resulting infewer silicone particles in the deliverable contents of the syringe andless opportunity for interaction between the lubricity layer and thecontents of the syringe. They can also address the issue of migration ofthe lubricity layer away from the point of lubrication, improving thelubricity of the interface between the syringe barrel and the plunger.For example, the break-free force can be reduced and the drag on themoving plunger can be reduced, or optionally both.

It is contemplated that when the solute retainer is broken, the soluteretainer will continue to adhere to the lubricity layer and the syringebarrel, which can inhibit any particles from being entrained in thedeliverable contents of the syringe.

Certain of these coatings will also provide manufacturing advantages,particularly if the barrier layer, lubricity layer and surface treatmentare applied in the same apparatus, for example the illustrated PECVDapparatus. Optionally, the SiO_(x) barrier layer, lubricity layer, andsurface treatment can all be applied in one PECVD apparatus, thusgreatly reducing the amount of handling necessary.

Further advantages can be obtained by forming the barrier layer,lubricity layer, and solute retainer using the same precursors andvarying the process. For example, an SiO_(x) gas barrier layer can beapplied using an OMCTS precursor under high power/high O₂ conditions,followed by applying a lubricity layer applied using an OMCTS precursorunder low power and/or in the substantial or complete absence of oxygen,finishing with a surface treatment using an OMCTS precursor underintermediate power and oxygen.

Syringe Having Barrel with SiO_(x) Coated Interior and Barrier CoatedExterior

In any embodiment, the thermoplastic base material optionally caninclude a polyolefin, for example polypropylene or a cyclic olefincopolymer (for example the material sold under the trademark TOPAS®), apolyester, for example polyethylene terephthalate, a polycarbonate, forexample a bisphenol A polycarbonate thermoplastic, or other materials.Composite syringe barrels are contemplated having any one of thesematerials as an outer layer and the same or a different one of thesematerials as an inner layer. Any of the material combinations of thecomposite syringe barrels or sample tubes described elsewhere in thisspecification can also be used.

In any embodiment, the resin optionally can include polyvinylidenechloride in homopolymer or copolymer form. For example, the PVdChomopolymers (trivial name: Saran) or copolymers described in U.S. Pat.No. 6,165,566, incorporated here by reference, can be employed. Theresin optionally can be applied onto the exterior surface of the barrelin the form of a latex or other dispersion.

In any embodiment, the syringe barrel 548 optionally can include alubricity layer disposed between the plunger and the barrier layer ofSiO_(x). Suitable lubricity layers are described elsewhere in thisspecification.

In any embodiment, the lubricity layer optionally can be applied byPECVD and optionally can include material characterized as defined inthe Definition Section.

In any embodiment, the syringe barrel 548 optionally can include asurface treatment covering the lubricity layer in an amount effective toreduce the leaching of the lubricity layer, constituents of thethermoplastic base material, or both into the lumen 604.

Method of Making Syringe Having Barrel with SiO_(x) Coated Interior andBarrier Coated Exterior

Even another embodiment is a method of making a syringe as described inany of the embodiments of this specification, including a plunger, abarrel, and interior and exterior barrier layers. A barrel is providedhaving an interior surface for receiving the plunger for sliding and anexterior surface. A barrier layer of SiO_(x) is provided on the interiorsurface of the barrel by PECVD. A barrier layer of a resin is providedon the exterior surface of the barrel. The plunger and barrel areassembled to provide a syringe.

For effective coating (uniform wetting) of the plastic article with theaqueous latex, it is contemplated to be useful to match the surfacetension of the latex to the plastic substrate. This can be accomplishedby several approaches, independently or combined, for example, reducingthe surface tension of the latex (with surfactants or solvents), and/orcorona pretreatment of the plastic article, and/or chemical priming ofthe plastic article.

The resin optionally can be applied via dip coating of the latex ontothe exterior surface of the barrel, spray coating of the latex onto theexterior surface of the barrel, or both, providing plastic-basedarticles offering improved gas and vapor barrier performance.Polyvinylidene chloride plastic laminate articles can be made thatprovide significantly improved gas barrier performance versus thenon-laminated plastic article.

In any embodiment, the resin optionally can be heat cured. The resinoptionally can be cured by removing water. Water can be removed by heatcuring the resin, exposing the resin to a partial vacuum or low-humidityenvironment, catalytically curing the resin, or other expedients.

An effective thermal cure schedule is contemplated to provide finaldrying to permit PVdC crystallization, offering barrier performance.Primary curing can be carried out at an elevated temperature, forexample between 180-310 .degree. F. (82-154 .degree. C.), of coursedepending on the heat tolerance of the thermoplastic base material.Barrier performance after the primary cure optionally can be about 85%of the ultimate barrier performance achieved after a final cure.

A final cure can be carried out at temperatures ranging from ambienttemperature, such as about 65-75 .degree. F. (18-24 .degree. C.) for along time (such as 2 weeks) to an elevated temperature, such as 122.degree. F. (50 .degree. C.), for a short time, such as four hours.

The PVdC-plastic laminate articles, in addition to superior barrierperformance, are optionally contemplated to provide one or moredesirable properties such as colorless transparency, good gloss,abrasion resistance, printability, and mechanical strain resistance.

Plungers with Barrier Coated Piston Front Face

Another embodiment is a plunger for a syringe, including a piston and apush rod. The piston has a front face, a generally cylindrical sideface, and a back portion, the side face being configured to movably seatwithin a syringe barrel. The front face has a barrier layer. The pushrod engages the back portion and is configured for advancing the pistonin a syringe barrel.

With Lubricity Layer Interfacing with Side Face

Yet another embodiment is a plunger for a syringe, including a piston, alubricity layer, and a push rod. The piston has a front face, agenerally cylindrical side face, and a back portion. The side face isconfigured to movably seat within a syringe barrel. The lubricity layerinterfaces with the side face. The push rod engages the back portion ofthe piston and is configured for advancing the piston in a syringebarrel.

Two Piece Syringe and Luer Fitting

Another embodiment is a syringe including a plunger, a syringe barrel,and a Luer fitting. The syringe includes a barrel having an interiorsurface receiving the plunger for sliding. The Luer fitting includes aLuer taper having an internal passage defined by an internal surface.The Luer fitting is formed as a separate piece from the syringe barreland joined to the syringe barrel by a coupling. The internal passage ofthe Luer taper has a barrier layer of SiO_(x).

Lubricant Compositions—Lubricity Layer Deposited from an OrganosiliconPrecursor Made by In Situ Polymerizing Organosilicon Precursor—Productby Process—and Lubricity

Still another embodiment is a lubricity layer. This coating can be ofthe type made by the following process.

Any of the precursors mentioned elsewhere in this specification can beused, alone or in combination. The precursor is applied to a substrateunder conditions effective to form a coating. The coating is polymerizedor crosslinked, or both, to form a lubricated surface having a lowerplunger sliding force or breakout force than the untreated substrate.

Another embodiment is a method of applying a lubricity layer. Anorganosilicon precursor is applied to a substrate under conditionseffective to form a coating. The coating is polymerized or crosslinked,or both, to form a lubricated surface having a lower plunger slidingforce or breakout force than the untreated substrate.

Product by Process and Analytical Properties

Even another aspect of the invention is a lubricity layer deposited byPECVD from a feed gas comprising an organometallic precursor, optionallyan organosilicon precursor, optionally a linear siloxane, a linearsilazane, a monocyclic siloxane, a monocyclic silazane, a polycyclicsiloxane, a polycyclic silazane, or any combination of two or more ofthese. The coating has a density between 1.25 and 1.65 g/cm³ optionallybetween 1.35 and 1.55 g/cm³, optionally between 1.4 and 1.5 g/cm³,optionally between 1.44 and 1.48 g/cm³ as determined by X-rayreflectivity (XRR).

Still another aspect of the invention is a lubricity layer deposited byPECVD from a feed gas comprising an organometallic precursor, optionallyan organosilicon precursor, optionally a linear siloxane, a linearsilazane, a monocyclic siloxane, a monocyclic silazane, a polycyclicsiloxane, a polycyclic silazane, or any combination of two or more ofthese. The coating has as an outgas component one or more oligomerscontaining repeating -(Me)₂SiO— moieties, as determined by gaschromatography/mass spectrometry. Optionally, the coating meets thelimitations of any of embodiments shown. Optionally, the coating outgascomponent as determined by gas chromatography/mass spectrometry issubstantially free of trimethylsilanol.

Optionally, the coating outgas component can be at least 10 ng/test ofoligomers containing repeating -(Me)₂SiO— moieties, as determined by gaschromatography/mass spectrometry using the following test conditions:

-   -   GC Column 30 m×0.25 mm DB-5MS (J&W Scientific), 0.25 μm film        thickness    -   Flow rate: 1.0 ml/min, constant flow mode    -   Detector: Mass Selective Detector (MSD)    -   Injection mode: Split injection (10:1 split ratio)    -   Outgassing Conditions: 1½″ (37 mm) Chamber, purge for three hour        at 85° C., Flow 60 ml/mn    -   Oven temperature 40° C. (5 min) to 300° C. at 10° C./min.; hold        for 5 min at 300° C.

Optionally, the outgas component can include at least 20 ng/test ofoligomers containing repeating -(Me)₂SiO— moieties.

Optionally, the feed gas comprises a monocyclic siloxane, a monocyclicsilazane, a polycyclic siloxane, a polycyclic silazane, or anycombination of two or more of these, for example a monocyclic siloxane,a monocyclic silazane, or any combination of two or more of these, forexample octamethylcyclotetrasiloxane.

The lubricity layer of any embodiment can have a thickness measured bytransmission electron microscopy (TEM) between 1 and 500 nm, optionallybetween 10 and 500 nm, optionally between 20 and 200 nm, optionallybetween 20 and 100 nm, optionally between 30 and 100 nm.

Another aspect of the invention is a lubricity layer deposited by PECVDfrom a feed gas comprising a monocyclic siloxane, a monocyclic silazane,a polycyclic siloxane, a polycyclic silazane, or any combination of twoor more of these. The coating has an atomic concentration of carbon,normalized to 100% of carbon, oxygen, and silicon, as determined byX-ray photoelectron spectroscopy (XPS), greater than the atomicconcentration of carbon in the atomic formula for the feed gas.Optionally, the coating meets the limitations of any embodiments.

Optionally, the atomic concentration of carbon increases by from 1 to 80atomic percent (as calculated and based on the XPS conditions in Example9), alternatively from 10 to 70 atomic percent, alternatively from 20 to60 atomic percent, alternatively from 30 to 50 atomic percent,alternatively from 35 to 45 atomic percent, alternatively from 37 to 41atomic percent.

An additional aspect of the invention is a lubricity layer deposited byPECVD from a feed gas comprising a monocyclic siloxane, a monocyclicsilazane, a polycyclic siloxane, a polycyclic silazane, or anycombination of two or more of these. The coating has an atomicconcentration of silicon, normalized to 100% of carbon, oxygen, andsilicon, as determined by X-ray photoelectron spectroscopy (XPS), lessthan the atomic concentration of silicon in the atomic formula for thefeed gas. Optionally, the coating meets the limitations of anyembodiments.

Optionally, the atomic concentration of silicon decreases by from 1 to80 atomic percent (as calculated and based on the XPS conditions inExample 9), alternatively from 10 to 70 atomic percent, alternativelyfrom 20 to 60 atomic percent, alternatively from 30 to 55 atomicpercent, alternatively from 40 to 50 atomic percent, alternatively from42 to 46 atomic percent.

Lubricity layers having combinations of any two or more propertiesrecited in this specification are also expressly contemplated.

Vessels Generally

A coated vessel or container as described herein and/or preparedaccording to a method described herein can be used for reception and/orstorage and/or delivery of a compound or composition. The compound orcomposition can be sensitive, for example air-sensitive,oxygen-sensitive, sensitive to humidity and/or sensitive to mechanicalinfluences. It can be a biologically active compound or composition, forexample a medicament like insulin or a composition comprising insulin.In another aspect, it can be a biological fluid, optionally a bodilyfluid, for example blood or a blood fraction. In certain aspects of thepresent invention, the compound or composition is a product to beadministrated to a subject in need thereof, for example a product to beinjected, like blood (as in transfusion of blood from a donor to arecipient or reintroduction of blood from a patient back to the patient)or insulin.

A coated vessel or container as described herein and/or preparedaccording to a method described herein can further be used forprotecting a compound or composition contained in its interior spaceagainst mechanical and/or chemical effects of the surface of theuncoated vessel material. For example, it can be used for preventing orreducing precipitation and/or clotting or platelet activation of thecompound or a component of the composition, for example insulinprecipitation or blood clotting or platelet activation.

It can further be used for protecting a compound or compositioncontained in its interior against the environment outside of the vessel,for example by preventing or reducing the entry of one or more compoundsfrom the environment surrounding the vessel into the interior space ofthe vessel. Such environmental compound can be a gas or liquid, forexample an atmospheric gas or liquid containing oxygen, air, and/orwater vapor.

A coated vessel as described herein can also be evacuated and stored inan evacuated state. For example, the coating allows better maintenanceof the vacuum in comparison to a corresponding uncoated vessel. In oneaspect of this embodiment, the coated vessel is a blood collection tube.The tube can also contain an agent for preventing blood clotting orplatelet activation, for example EDTA or heparin.

Any of the above-described embodiments can be made, for example, byproviding as the vessel a length of tubing from about 1 cm to about 200cm, optionally from about 1 cm to about 150 cm, optionally from about 1cm to about 120 cm, optionally from about 1 cm to about 100 cm,optionally from about 1 cm to about 80 cm, optionally from about 1 cm toabout 60 cm, optionally from about 1 cm to about 40 cm, optionally fromabout 1 cm to about 30 cm long, and processing it with a probe electrodeas described below. Particularly for the longer lengths in the aboveranges, it is contemplated that relative motion between the probe andthe vessel can be useful during coating formation. This can be done, forexample, by moving the vessel with respect to the probe or moving theprobe with respect to the vessel.

In these embodiments, it is contemplated that the coating can be thinneror less complete than can be preferred for a barrier layer, as thevessel in some embodiments will not require the high barrier integrityof an evacuated blood collection tube.

As an optional feature of any of the foregoing embodiments the vesselhas a central axis.

As an optional feature of any of the foregoing embodiments the vesselwall is sufficiently flexible to be flexed at least once at 20 .degree.C., without breaking the wall, over a range from at least substantiallystraight to a bending radius at the central axis of not more than 100times as great as the outer diameter of the vessel.

As an optional feature of any of the foregoing embodiments the bendingradius at the central axis is not more than 90 times as great as, or notmore than 80 times as great as, or not more than 70 times as great as,or not more than 60 times as great as, or not more than 50 times asgreat as, or not more than 40 times as great as, or not more than 30times as great as, or not more than 20 times as great as, or not morethan 10 times as great as, or not more than 9 times as great as, or notmore than 8 times as great as, or not more than 7 times as great as, ornot more than 6 times as great as, or not more than 5 times as great as,or not more than 4 times as great as, or not more than 3 times as greatas, or not more than 2 times as great as, or not more than, the outerdiameter of the vessel.

As an optional feature of any of the foregoing embodiments the vesselwall can be a fluid-contacting surface made of flexible material.

As an optional feature of any of the foregoing embodiments the vessellumen can be the fluid flow passage of a pump.

As an optional feature of any of the foregoing embodiments the vesselcan be a blood bag adapted to maintain blood in good condition formedical use.

As an optional feature of any of the foregoing embodiments the polymericmaterial can be a silicone elastomer or a thermoplastic polyurethane, astwo examples, or any material suitable for contact with blood, or withinsulin.

In an optional embodiment, the vessel has an inner diameter of at least2 mm, or at least 4 mm.

As an optional feature of any of the foregoing embodiments the vessel isa tube.

As an optional feature of any of the foregoing embodiments the lumen hasat least two open ends.

Vessel Containing Viable Blood, Having a Coating of Group III or IVElement

Another embodiment is a blood containing vessel having a wall having aninner surface defining a lumen. The inner surface has an at leastpartial coating of a composition comprising one or more elements ofGroup III, one or more elements of Group IV, or a combination of two ormore of these. The thickness of the coating is between monomolecularthickness and about 1000 nm thick, inclusive, on the inner surface. Thevessel contains blood viable for return to the vascular system of apatient disposed within the lumen in contact with the layer.

Coating of Group III or IV Element Reduces Clotting or PlateletActivation of Blood in the Vessel

Optionally, in the vessel of the preceding paragraph, the coating of theGroup III or IV Element is effective to reduce the clotting or plateletactivation of blood exposed to the inner surface of the vessel wall.

Pharmaceutical Delivery Vessels

A coated vessel or container as described herein can be used forpreventing or reducing the escape of a compound or composition containedin the vessel into the environment surrounding the vessel.

Further uses of the coating and vessel as described herein, which areapparent from any part of the description and claims, are alsocontemplated.

Vessel Containing Insulin, Having a Coating of Group III or IV Element

Another embodiment is an insulin containing vessel including a wallhaving an inner surface defining a lumen. The inner surface has an atleast partial coating of a composition comprising carbon, one or moreelements of Group III, one or more elements of Group IV, or acombination of two or more of these. The coating can be frommonomolecular thickness to about 1000 nm thick on the inner surface.Insulin is disposed within the lumen in contact with the coating.

Coating of Group III or IV Element Reduces Precipitation of Insulin inthe Vessel

Optionally, in the vessel of the preceding paragraph, the coating of acomposition comprising carbon, one or more elements of Group III, one ormore elements of Group IV, or a combination of two or more of these, iseffective to reduce the formation of a precipitate from insulincontacting the inner surface, compared to the same surface absent thecoating.

WORKING EXAMPLES

Basic Protocols for Forming and Coating Tubes and Syringe Barrels

The vessels tested in the subsequent working examples were formed andcoated according to the following exemplary protocols, except asotherwise indicated in individual examples. Particular parameter valuesgiven in the following basic protocols, e.g. the electric power andprocess gas flow, are typical values. Whenever parameter values werechanged in comparison to these typical values, this will be indicated inthe subsequent working examples. The same applies to the type andcomposition of the process gas.

Protocol for Forming COC Tube

Cyclic olefin copolymer (COC) tubes of the shape and size commonly usedas evacuated blood collection tubes (“COC tubes”) were injection moldedfrom Topas®8007-04 cyclic olefin copolymer (COC) resin, available fromHoechst AG, Frankfurt am Main, Germany, having these dimensions: 75 mmlength, 13 mm outer diameter, and 0.85 mm wall thickness, each having avolume of about 7.25 cm³ and a closed, rounded end.

Protocol for Forming PET Tube

Polyethylene terephthalate (PET) tubes of the type commonly used asevacuated blood collection tubes (“PET tubes”) were injection molded inthe same mold used for the Protocol for Forming COC Tube, having thesedimensions: 75 mm length, 13 mm outer diameter, and 0.85 mm wallthickness, each having a volume of about 7.25 cm³ and a closed, roundedend.

Protocol for Coating Tube Interior with SiO_(x)

The apparatus as shown in FIG. 2 was used. The vessel holder 50 was madefrom Delrin® acetal resin, available from E.I. du Pont de Nemours andCo., Wilmington Del., USA, with an outside diameter of 1.75 inches (44mm) and a height of 1.75 inches (44 mm). The vessel holder 50 was housedin a Delrin® structure that allowed the device to move in and out of theelectrode (160).

The electrode 160 was made from copper with a Delrin® shield. TheDelrin® shield was conformal around the outside of the copper electrode160. The electrode 160 measured approximately 3 inches (76 mm) high(inside) and was approximately 0.75 inches (19 mm) wide.

The tube used as the vessel 80 was inserted into the vessel holder 50base sealing with Viton® O-rings 490, 504 (Viton® is a trademark ofDuPont Performance Elastomers LLC, Wilmington Del., USA) around theexterior of the tube. The tube 80 was carefully moved into the sealingposition over the extended (stationary) ⅛-inch (3-mm) diameter brassprobe or counter electrode 108 and pushed against a copper plasmascreen.

The copper plasma screen was a perforated copper foil material (K&SEngineering, Chicago Ill., USA, Part #LXMUW5 copper mesh) cut to fit theoutside diameter of the tube, and was held in place by a radiallyextending abutment surface that acted as a stop for the tube insertion.Two pieces of the copper mesh were fit snugly around the brass probe orcounter electrode 108, insuring good electrical contact.

The brass probe or counter electrode 108 extended approximately 70 mminto the interior of the tube and had an array of #80 wire(diameter=0.0135 inch or 0.343 mm). The brass probe or counter electrode108 extended through a Swagelok® fitting (available from Swagelok Co.,Solon Ohio, USA) located at the bottom of the vessel holder 50,extending through the vessel holder 50 base structure. The brass probeor counter electrode 108 was grounded to the casing of the RF matchingnetwork.

The gas delivery port 110 was 12 holes in the probe or counter electrode108 along the length of the tube (three on each of four sides oriented90 degrees from each other) and two holes in the aluminum cap thatplugged the end of the gas delivery port 110. The gas delivery port 110was connected to a stainless steel assembly comprised of Swagelok®fittings incorporating a manual ball valve for venting, a thermocouplepressure gauge and a bypass valve connected to the vacuum pumping line.In addition, the gas system was connected to the gas delivery port 110allowing the process gases, oxygen and hexamethyldisiloxane (HMDSO) tobe flowed through the gas delivery port 110 (under process pressures)into the interior of the tube.

The gas system was comprised of a Aalborg® GFC17 mass flow meter (Part #EW-32661-34, Cole-Parmer Instrument Co., Barrington Ill. USA) forcontrollably flowing oxygen at 90 sccm (or at the specific flow reportedfor a particular example) into the process and a polyether ether ketone(“PEEK”) capillary (outside diameter, “OD” 1/16-inch (1.5-mm.), insidediameter, “ID” 0.004 inch (0.1 mm)) of length 49.5 inches (1.26 m). ThePEEK capillary end was inserted into liquid hexamethyldisiloxane(“HMDSO,” Alfa Aesar® Part Number L16970, NMR Grade, available fromJohnson Matthey PLC, London). The liquid HMDSO was pulled through thecapillary due to the lower pressure in the tube during processing. TheHMDSO was then vaporized into a vapor at the exit of the capillary as itentered the low pressure region.

To ensure no condensation of the liquid HMDSO past this point, the gasstream (including the oxygen) was diverted to the pumping line when itwas not flowing into the interior of the tube for processing via aSwagelok® 3-way valve. Once the tube was installed, the vacuum pumpvalve was opened to the vessel holder 50 and the interior of the tube.

An Alcatel rotary vane vacuum pump and blower comprised the vacuum pumpsystem. The pumping system allowed the interior of the tube to bereduced to pressure(s) of less than 200 mTorr while the process gaseswere flowing at the indicated rates.

Once the base vacuum level was achieved, the vessel holder 50 assemblywas moved into the electrode 160 assembly. The gas stream (oxygen andHMDSO vapor) was flowed into the brass gas delivery port 110 (byadjusting the 3-way valve from the pumping line to the gas delivery port110). Pressure inside the tube was approximately 300 mTorr as measuredby a capacitance manometer (MKS) installed on the pumping line near thevalve that controlled the vacuum. In addition to the tube pressure, thepressure inside the gas delivery port 110 and gas system was alsomeasured with the thermocouple vacuum gauge that was connected to thegas system. This pressure was typically less than 8 Torr.

Once the gas was flowing to the interior of the tube, the RF powersupply was turned on to its fixed power level. A ENI ACG-6 600 Watt RFpower supply was used (at 13.56 MHz) at a fixed power level ofapproximately 50 Watts. The output power was calibrated in this and allfollowing Protocols and Examples using a Bird Corporation Model 43 RFWatt meter connected to the RF output of the power supply duringoperation of the coating apparatus. The following relationship was foundbetween the dial setting on the power supply and the output power: RFPower Out=55.times.Dial Setting. In the priority applications to thepresent application, a factor 100 was used, which was incorrect. The RFpower supply was connected to a COMDEL CPMX1000 auto match which matchedthe complex impedance of the plasma (to be created in the tube) to the50 ohm output impedance of the ENI ACG-6 RF power supply. The forwardpower was 50 Watts (or the specific amount reported for a particularexample) and the reflected power was 0 Watts so that the applied powerwas delivered to the interior of the tube. The RF power supply wascontrolled by a laboratory timer and the power on time set to 5 seconds(or the specific time period reported for a particular example). Uponinitiation of the RF power, a uniform plasma was established inside theinterior of the tube. The plasma was maintained for the entire 5 secondsuntil the RF power was terminated by the timer. The plasma produced asilicon oxide coating of approximately 20 nm thickness (or the specificthickness reported in a particular example) on the interior of the tubesurface.

After coating, the gas flow was diverted back to the vacuum line and thevacuum valve was closed. The vent valve was then opened, returning theinterior of the tube to atmospheric pressure (approximately 760 Torr).The tube was then carefully removed from the vessel holder 50 assembly(after moving the vessel holder 50 assembly out of the electrode 160assembly).

Protocol for Forming COC Syringe Barrel

Syringe barrels (“COC syringe barrels”), CV Holdings Part 11447, eachhaving a 2.8 mL overall volume (excluding the Luer fitting) and anominal 1 mL delivery volume or plunger displacement, Luer adapter type,were injection molded from Topas® 8007-04 cyclic olefin copolymer (COC)resin, available from Hoechst AG, Frankfurt am Main, Germany, havingthese dimensions: about 51 mm overall length, 8.6 mm inner syringebarrel diameter and 1.27 mm wall thickness at the cylindrical portion,with an integral 9.5 millimeter length needle capillary Luer adaptermolded on one end and two finger flanges molded near the other end.

Protocol for Coating COC Syringe Barrel Interior with SiO_(x)

An injection molded COC syringe barrel was interior coated with SiO_(x).The apparatus as shown in FIG. 2 was modified to hold a COC syringebarrel with butt sealing at the base of the COC syringe barrel.Additionally a cap was fabricated out of a stainless steel Luer fittingand a polypropylene cap that sealed the end of the COC syringe barrel,allowing the interior of the COC syringe barrel to be evacuated.

The vessel holder 50 was made from Delrin® with an outside diameter of1.75 inches (44 mm) and a height of 1.75 inches (44 mm). The vesselholder 50 was housed in a Delrin® structure that allowed the device tomove in and out of the electrode 160.

The electrode 160 was made from copper with a Delrin® shield. TheDelrin® shield was conformal around the outside of the copper electrode160. The electrode 160 measured approximately 3 inches (76 mm) high(inside) and was approximately 0.75 inches (19 mm) wide. The COC syringebarrel was inserted into the vessel holder 50, base sealing with anViton® O-rings.

The COC syringe barrel was carefully moved into the sealing positionover the extended (stationary) ⅛-inch (3-mm.) diameter brass probe orcounter electrode 108 and pushed against a copper plasma screen. Thecopper plasma screen was a perforated copper foil material (K&SEngineering Part #LXMUW5 Copper mesh) cut to fit the outside diameter ofthe COC syringe barrel and was held in place by a abutment surface thatacted as a stop for the COC syringe barrel insertion. Two pieces of thecopper mesh were fit snugly around the brass probe or counter electrode108 insuring good electrical contact.

The probe or counter electrode 108 extended approximately 20 mm into theinterior of the COC syringe barrel and was open at its end. The brassprobe or counter electrode 108 extended through a Swagelok® fittinglocated at the bottom of the vessel holder 50, extending through thevessel holder 50 base structure. The brass probe or counter electrode108 was grounded to the casing of the RF matching network.

The gas delivery port 110 was connected to a stainless steel assemblycomprised of Swagelok® fittings incorporating a manual ball valve forventing, a thermocouple pressure gauge and a bypass valve connected tothe vacuum pumping line. In addition, the gas system was connected tothe gas delivery port 110 allowing the process gases, oxygen andhexamethyldisiloxane (HMDSO) to be flowed through the gas delivery port110 (under process pressures) into the interior of the COC syringebarrel.

The gas system was comprised of a Aalborg® GFC17 mass flow meter (ColeParmer Part # EW-32661-34) for controllably flowing oxygen at 90 sccm(or at the specific flow reported for a particular example) into theprocess and a PEEK capillary (OD 1/16-inch (3-mm) ID 0.004 inches (0.1mm)) of length 49.5 inches (1.26 m). The PEEK capillary end was insertedinto liquid hexamethyldisiloxane (Alfa Aesar® Part Number L16970, NMRGrade). The liquid HMDSO was pulled through the capillary due to thelower pressure in the COC syringe barrel during processing. The HMDSOwas then vaporized into a vapor at the exit of the capillary as itentered the low pressure region.

To ensure no condensation of the liquid HMDSO past this point, the gasstream (including the oxygen) was diverted to the pumping line when itwas not flowing into the interior of the COC syringe barrel forprocessing via a Swagelok® 3-way valve.

Once the COC syringe barrel was installed, the vacuum pump valve wasopened to the vessel holder 50 and the interior of the COC syringebarrel. An Alcatel rotary vane vacuum pump and blower comprised thevacuum pump system. The pumping system allowed the interior of the COCsyringe barrel to be reduced to pressure(s) of less than 150 mTorr whilethe process gases were flowing at the indicated rates. A lower pumpingpressure was achievable with the COC syringe barrel, as opposed to thetube, because the COC syringe barrel has a much smaller internal volume.

After the base vacuum level was achieved, the vessel holder 50 assemblywas moved into the electrode 160 assembly. The gas stream (oxygen andHMDSO vapor) was flowed into the brass gas delivery port 110 (byadjusting the 3-way valve from the pumping line to the gas delivery port110). The pressure inside the COC syringe barrel was approximately 200mTorr as measured by a capacitance manometer (MKS) installed on thepumping line near the valve that controlled the vacuum. In addition tothe COC syringe barrel pressure, the pressure inside the gas deliveryport 110 and gas system was also measured with the thermocouple vacuumgauge that was connected to the gas system. This pressure was typicallyless than 8 Torr.

When the gas was flowing to the interior of the COC syringe barrel, theRF power supply was turned on to its fixed power level. A ENI ACG-6 600Watt RF power supply was used (at 13.56 MHz) at a fixed power level ofapproximately 30 Watts. The RF power supply was connected to a COMDELCPMX1000 auto match that matched the complex impedance of the plasma (tobe created in the COC syringe barrel) to the 50 ohm output impedance ofthe ENI ACG-6 RF power supply. The forward power was 30 Watts (orwhatever value is reported in a working example) and the reflected powerwas 0 Watts so that the power was delivered to the interior of the COCsyringe barrel. The RF power supply was controlled by a laboratory timerand the power on time set to 5 seconds (or the specific time periodreported for a particular example).

Upon initiation of the RF power, a uniform plasma was established insidethe interior of the COC syringe barrel. The plasma was maintained forthe entire 5 seconds (or other coating time indicated in a specificexample) until the RF power was terminated by the timer. The plasmaproduced a silicon oxide coating of approximately 20 nm thickness (orthe thickness reported in a specific example) on the interior of the COCsyringe barrel surface.

After coating, the gas flow was diverted back to the vacuum line and thevacuum valve was closed. The vent valve was then opened, returning theinterior of the COC syringe barrel to atmospheric pressure(approximately 760 Torr). The COC syringe barrel was then carefullyremoved from the vessel holder 50 assembly (after moving the vesselholder 50 assembly out of the electrode 160 assembly).

Protocol for Coating COC Syringe Barrel Interior with OMCTS LubricityLayer

COC syringe barrels as previously identified were interior coated with alubricity layer. The apparatus as shown in FIG. 2 was modified to hold aCOC syringe barrel with butt sealing at the base of the COC syringebarrel. Additionally a cap was fabricated out of a stainless steel Luerfitting and a polypropylene cap that sealed the end of the COC syringebarrel. The installation of a Buna-N O-ring onto the Luer fittingallowed a vacuum tight seal, allowing the interior of the COC syringebarrel to be evacuated.

The vessel holder 50 was made from Delrin® with an outside diameter of1.75 inches (44 mm) and a height of 1.75 inches (44 mm). The vesselholder 50 was housed in a Delrin® structure that allowed the device tomove in and out of the electrode 160.

The electrode 160 was made from copper with a Delrin® shield. TheDelrin® shield was conformal around the outside of the copper electrode160. The electrode 160 measured approximately 3 inches (76 mm) high(inside) and was approximately 0.75 inches (19 mm) wide. The COC syringebarrel was inserted into the vessel holder 50, base sealing with Viton®O-rings around the bottom of the finger flanges and lip of the COCsyringe barrel.

The COC syringe barrel was carefully moved into the sealing positionover the extended (stationary) ⅛-inch (3-mm.) diameter brass probe orcounter electrode 108 and pushed against a copper plasma screen. Thecopper plasma screen was a perforated copper foil material (K&SEngineering Part #LXMUW5 Copper mesh) cut to fit the outside diameter ofthe COC syringe barrel and was held in place by a abutment surface 494that acted as a stop for the COC syringe barrel insertion. Two pieces ofthe copper mesh were fit snugly around the brass probe or counterelectrode 108 insuring good electrical contact.

The probe or counter electrode 108 extended approximately 20 mm (unlessotherwise indicated) into the interior of the COC syringe barrel and wasopen at its end. The brass probe or counter electrode 108 extendedthrough a Swagelok® fitting located at the bottom of the vessel holder50, extending through the vessel holder 50 base structure. The brassprobe or counter electrode 108 was grounded to the casing of the RFmatching network.

The gas delivery port 110 was connected to a stainless steel assemblycomprised of Swagelok® fittings incorporating a manual ball valve forventing, a thermocouple pressure gauge and a bypass valve connected tothe vacuum pumping line. In addition, the gas system was connected tothe gas delivery port 110 allowing the process gas,octamethylcyclotetrasiloxane (OMCTS) (or the specific process gasreported for a particular example) to be flowed through the gas deliveryport 110 (under process pressures) into the interior of the COC syringebarrel.

The gas system was comprised of a commercially available HoribaVC1310/SEF8240 OMCTS10SC 4CR heated mass flow vaporization system thatheated the OMCTS to about 100 .degree. C. The Horiba system wasconnected to liquid octamethylcyclotetrasiloxane (Alfa Aesar® PartNumber A12540, 98%) through a ⅛-inch (3-mm) outside diameter PFA tubewith an inside diameter of 1/16 in (1.5 mm). The OMCTS flow rate was setto 1.25 sccm (or the specific organosilicon precursor flow reported fora particular example). To ensure no condensation of the vaporized OMCTSflow past this point, the gas stream was diverted to the pumping linewhen it was not flowing into the interior of the COC syringe barrel forprocessing via a Swagelok® 3-way valve.

Once the COC syringe barrel was installed, the vacuum pump valve wasopened to the vessel holder 50 and the interior of the COC syringebarrel. An Alcatel rotary vane vacuum pump and blower comprised thevacuum pump system. The pumping system allowed the interior of the COCsyringe barrel to be reduced to pressure(s) of less than 100 mTorr whilethe process gases were flowing at the indicated rates. A lower pressurecould be obtained in this instance, compared to the tube and previousCOC syringe barrel examples, because the overall process gas flow rateis lower in this instance.

Once the base vacuum level was achieved, the vessel holder 50 assemblywas moved into the electrode 160 assembly. The gas stream (OMCTS vapor)was flowed into the brass gas delivery port 110 (by adjusting the 3-wayvalve from the pumping line to the gas delivery port 110). Pressureinside the COC syringe barrel was approximately 140 mTorr as measured bya capacitance manometer (MKS) installed on the pumping line near thevalve that controlled the vacuum. In addition to the COC syringe barrelpressure, the pressure inside the gas delivery port 110 and gas systemwas also measured with the thermocouple vacuum gauge that was connectedto the gas system. This pressure was typically less than 6 Torr.

Once the gas was flowing to the interior of the COC syringe barrel, theRF power supply was turned on to its fixed power level. A ENI ACG-6 600Watt RF power supply was used (at 13.56 MHz) at a fixed power level ofapproximately 7.5 Watts (or other power level indicated in a specificexample). The RF power supply was connected to a COMDEL CPMX1000 automatch which matched the complex impedance of the plasma (to be createdin the COC syringe barrel) to the 50 ohm output impedance of the ENIACG-6 RF power supply. The forward power was 7.5 Watts and the reflectedpower was 0 Watts so that 7.5 Watts of power (or a different power leveldelivered in a given example) was delivered to the interior of the COCsyringe barrel. The RF power supply was controlled by a laboratory timerand the power on time set to 10 seconds (or a different time stated in agiven example).

Upon initiation of the RF power, a uniform plasma was established insidethe interior of the COC syringe barrel. The plasma was maintained forthe entire coating time, until the RF power was terminated by the timer.The plasma produced a lubricity layer on the interior of the COC syringebarrel surface.

After coating, the gas flow was diverted back to the vacuum line and thevacuum valve was closed. The vent valve was then opened, returning theinterior of the COC syringe barrel to atmospheric pressure(approximately 760 Torr). The COC syringe barrel was then carefullyremoved from the vessel holder 50 assembly (after moving the vesselholder 50 assembly out of the electrode 160 assembly).

Protocol for Coating COC Syringe Barrel Interior with HMDSO Coating

The Protocol for Coating COC Syringe Barrel Interior with OMCTSLubricity layer was also used for applying an HMDSO coating, exceptsubstituting HMDSO for OMCTS.

Example 1

In the following test, hexamethyldisiloxane (HMDSO) was used as theorganosilicon (“O—Si”) feed to PECVD apparatus of FIG. 2 to apply anSiO_(x) coating on the internal surface of a cyclic olefin copolymer(COC) tube as described in the Protocol for Forming COC Tube. Thedeposition conditions are summarized in the Protocol for Coating TubeInterior with SiO_(x) and Table 1. The control was the same type of tubeto which no barrier layer was applied. The coated and uncoated tubeswere then tested for their oxygen transmission rate (OTR) and theirwater vapor transmission rate (WVTR).

Referring to Table 1, the uncoated COC tube had an OTR of 0.215cc/tube/day. Tubes A and B subjected to PECVD for 14 seconds had anaverage OTR of 0.0235 cc/tube/day. These results show that the SiO_(x)coating provided an oxygen transmission BIF over the uncoated tube of9.1. In other words, the SiO_(x) barrier layer reduced the oxygentransmission through the tube to less than one ninth its value withoutthe coating.

Tube C subjected to PECVD for 7 seconds had an OTR of 0.026. This resultshows that the SiO_(x) coating provided an OTR BIF over the uncoatedtube of 8.3. In other words, the SiO_(x) barrier layer applied in 7seconds reduced the oxygen transmission through the tube to less thanone eighth of its value without the coating.

The relative WVTRs of the same barrier layers on COC tubes were alsomeasured. The uncoated COC tube had a WVTR of 0.27 mg/tube/day. Tubes Aand B subjected to PECVD for 14 seconds had an average WVTR of 0.10mg/tube/day or less. Tube C subjected to PECVD for 7 seconds had a WVTRof 0.10 mg/tube/day. This result shows that the SiO_(x) coating provideda water vapor transmission barrier improvement factor (WVTR BIF) overthe uncoated tube of about 2.7. This was a surprising result, since theuncoated COC tube already has a very low WVTR.

Example 2

A series of PET tubes, made according to the Protocol for Forming PETTube, were coated with SiO_(x) according to the Protocol for CoatingTube Interior with SiO_(x) under the conditions reported in Table 2.Controls were made according to the Protocol for Forming PET Tube, butleft uncoated. OTR and WVTR samples of the tubes were prepared byepoxy-sealing the open end of each tube to an aluminum adaptor.

In a separate test, using the same type of coated PET tubes, mechanicalscratches of various lengths were induced with a steel needle throughthe interior coating, and the OTR BIF was tested. Controls were eitherleft uncoated or were the same type of coated tube without an inducedscratch. The OTR BIF, while diminished, was still improved over uncoatedtubes (Table 3).

Tubes were tested for OTR as follows. Each sample/adaptor assembly wasfitted onto a MOCON® Oxtran 2/21 Oxygen Permeability Instrument. Sampleswere allowed to equilibrate to transmission rate steady state (1-3 days)under the following test conditions:

-   -   Test Gas: Oxygen    -   Test Gas Concentration: 100%    -   Test Gas Humidity: 0% relative humidity    -   Test Gas Pressure: 760 mmHg    -   Test Temperature: 23.0 .degree. C. (73.4 .degree. F.)    -   Carrier Gas: 98% nitrogen, 2% hydrogen    -   Carrier Gas Humidity: 0% relative humidity

The OTR is reported as average of two determinations in Table 2.

Tubes were tested for WVTR as follows. The sample/adaptor assembly wasfitted onto a MOCON® Permatran-W 3/31 Water Vapor PermeabilityInstrument. Samples were allowed to equilibrate to transmission ratesteady state (1-3 days) under the following test conditions:

-   -   Test Gas: Water Vapor    -   Test Gas Concentration: NA    -   Test Gas Humidity: 100% relative humidity    -   Test Gas Temperature: 37.8 (.degree. C.) 100.0 (.degree. F.)    -   Carrier Gas: Dry nitrogen    -   Carrier Gas Humidity: 0% relative humidity

The WVTR is reported as average of two determinations in Table 2.

Example 3

A series of syringe barrels were made according to the Protocol forForming COC Syringe barrel. The syringe barrels were either barriercoated with SiO_(x) or not under the conditions reported in the Protocolfor Coating COC Syringe barrel Interior with SiO_(x) modified asindicated in Table 4.

OTR and WVTR samples of the syringe barrels were prepared byepoxy-sealing the open end of each syringe barrel to an aluminumadaptor. Additionally, the syringe barrel capillary ends were sealedwith epoxy. The syringe-adapter assemblies were tested for OTR or WVTRin the same manner as the PET tube samples, again using a MOCON® Oxtran2/21 Oxygen Permeability Instrument and a MOCON® Permatran-W 3/31 WaterVapor Permeability Instrument. The results are reported in Table 4.

Example 4

Composition Measurement of Plasma Coatings Using X-Ray PhotoelectronSpectroscopy (XPS)/Electron Spectroscopy for Chemical Analysis (ESCA)Surface Analysis

PET tubes made according to the Protocol for Forming PET Tube and coatedaccording to the Protocol for Coating Tube Interior with SiO_(x) werecut in half to expose the inner tube surface, which was then analyzedusing X-ray photoelectron spectroscopy (XPS).

The XPS data was quantified using relative sensitivity factors and amodel which assumes a homogeneous layer. The analysis volume is theproduct of the analysis area (spot size or aperture size) and the depthof information. Photoelectrons are generated within the X-raypenetration depth (typically many microns), but only the photoelectronswithin the top three photoelectron escape depths are detected. Escapedepths are on the order of 15-35 .ANG., which leads to an analysis depthof .about.50-100 .ANG. Typically, 95% of the signal originates fromwithin this depth.

Table 6 provides the atomic ratios of the elements detected. Theanalytical parameters used in for XPS are as follows:

Instrument PHI Quantum 2000 X-ray source Monochromated Alk_(α) 1486.6 eVAcceptance Angle ±23° Take-off angle 45° Analysis area 600 μm ChargeCorrection C1s 284.8 eV Ion Gun Conditions Ar⁺, 1 keV, 2 × 2 mm rasterSputter Rate 15.6 Å/min (SiO₂ Equivalent)

XPS does not detect hydrogen or helium. Values given are normalized toSi=1 for the experimental number (last row) using the elements detected,and to O=1 for the uncoated polyethylene terephthalate calculation andexample. Detection limits are approximately 0.05 to 1.0 atomic percent.Values given are alternatively normalized to 100% Si+O+C atoms.

The Inventive Example has an Si/O ratio of 2.4 indicating an SiO_(x)composition, with some residual carbon from incomplete oxidation of thecoating. This analysis demonstrates the composition of an SiO_(x)barrier layer applied to a polyethylene terephthalate tube according tothe present invention.

Table 5 shows the thickness of the SiO_(x) samples, determined using TEMaccording to the following method. Samples were prepared for Focused IonBeam (FIB) cross-sectioning by coating the samples with a sputteredlayer of platinum (50-100 nm thick) using a K575X Emitech coatingsystem. The coated samples were placed in an FEI FIB200 FIB system. Anadditional layer of platinum was FIB-deposited by injection of anorganometallic gas while rastering the 30 kV gallium ion beam over thearea of interest. The area of interest for each sample was chosen to bea location half way down the length of the tube. Thin cross sectionsmeasuring approximately 15 .mu.m (“micrometers”) long, 2 .mu.m wide and15 .mu.m deep were extracted from the die surface using a proprietaryin-situ FIB lift-out technique. The cross sections were attached to a200 mesh copper TEM grid using FIB-deposited platinum. One or twowindows in each section, measuring about 8 .mu.m wide, were thinned toelectron transparency using the gallium ion beam of the FEI FIB.

Cross-Sectional Image Analysis of the Prepared Samples was PerformedUtilizing a Transmission Electron Microscope (TEM). The Imaging Data wasRecorded Digitally.

The sample grids were transferred to a Hitachi HF2000 transmissionelectron microscope. Transmitted electron images were acquired atappropriate magnifications. The relevant instrument settings used duringimage acquisition are given below.

Transmission Instrument Electron Microscope Manufacturer/Model HitachiHF2000 Accelerating Voltage 200 kV Condenser Lens 1 0.78 Condenser Lens2 0 Objective Lens 6.34 Condenser Lens Aperture #1 Objective LensAperture for #3 imaging Selective Area Aperture for N/A SAD

Example 5

Plasma Uniformity

COC syringe barrels made according to the Protocol for Forming COCSyringe barrel were treated using the Protocol for Coating COC SyringeBarrel Interior with SiO_(x), with the following variations. Threedifferent modes of plasma generation were tested for coating syringebarrels such as 250 with SiO_(x) films. In Mode 1, hollow cathode plasmaignition was generated in the gas inlet 310, restricted area 292 andprocessing vessel lumen 304, and ordinary or non-hollow-cathode plasmawas generated in the remainder of the vessel lumen 300.

In Mode 2, hollow cathode plasma ignition was generated in therestricted area 292 and processing vessel lumen 304, and ordinary ornon-hollow-cathode plasma was generated in the remainder of the vessellumen 300 and gas inlet 310.

In Mode 3, ordinary or non-hollow-cathode plasma was generated in theentire vessel lumen 300 and gas inlet 310. This was accomplished byramping up power to quench any hollow cathode ignition. Table 7 showsthe conditions used to achieve these modes.

The syringe barrels 250 were then exposed to a ruthenium oxide stainingtechnique. The stain was made from sodium hypochlorite bleach andRu^((III)) chloride hydrate. 0.2 g of Ru^((III)) chloride hydrate wasput into a vial. 10 ml bleach were added and mixed thoroughly until theRu^((III)) chloride hydrate dissolved.

Each syringe barrel was sealed with a plastic Luer seal and 3 drops ofthe staining mixture were added to each syringe barrel. The syringebarrels were then sealed with aluminum tape and allowed to sit for 30-40minutes. In each set of syringe barrels tested, at least one uncoatedsyringe barrel was stained. The syringe barrels were stored with therestricted area 292 facing up.

Based on the staining, the following conclusions were drawn:

1. The stain started to attack the uncoated (or poorly coated) areaswithin 0.25 hours of exposure.

2. Ignition in the restricted area 292 resulted in SiO_(x) coating ofthe restricted area 292.

3. The best syringe barrel was produced by the test with no hollowcathode plasma ignition in either the gas inlet 310 or the restrictedarea 292. Only the restricted opening 294 was stained, most likely dueto leaking of the stain.

4. Staining is a good qualitative tool to guide uniformity work.

Based on all of the above, we concluded:

1. Under the conditions of the test, hollow cathode plasma in either thegas inlet 310 or the restricted area 292 led to poor uniformity of thecoating.

2. The best uniformity was achieved with no hollow cathode plasma ineither the gas inlet 310 or the restricted area 292.

Example 6

Lubricity Layers

The following materials were used in this test:

-   -   Commercial (BD Hypak® PRTC) glass prefillable syringes with        Luer-lok® tip) (ca 1 mL)    -   COC syringe barrels made according to the Protocol for Forming        COC Syringe barrel;    -   Commercial plastic syringe plungers with elastomeric tips taken        from Becton Dickinson Product No. 306507 (obtained as saline        prefilled syringes);    -   Normal saline solution (taken from the Becton-Dickinson Product        No. 306507 prefilled syringes);    -   Dillon Test Stand with an Advanced Force Gauge (Model AFG-50N)    -   Syringe holder and drain jig (fabricated to fit the Dillon Test        Stand)

The following procedure was used in this test.

The jig was installed on the Dillon Test Stand. The platform probemovement was adjusted to 6 in/min (2.5 mm/sec) and upper and lower stoplocations were set. The stop locations were verified using an emptysyringe and barrel. The commercial saline-filled syringes were labeled,the plungers were removed, and the saline solution was drained via theopen ends of the syringe barrels for re-use. Extra plungers wereobtained in the same manner for use with the COC and glass barrels.

Syringe plungers were inserted into the COC syringe barrels so that thesecond horizontal molding point of each plunger was even with thesyringe barrel lip (about 10 mm from the tip end). Using another syringeand needle assembly, the test syringes were filled via the capillary endwith 2-3 milliliters of saline solution, with the capillary enduppermost. The sides of the syringe were tapped to remove any large airbubbles at the plunger/fluid interface and along the walls, and any airbubbles were carefully pushed out of the syringe while maintaining theplunger in its vertical orientation.

Each filled syringe barrel/plunger assembly was installed into thesyringe jig. The test was initiated by pressing the down switch on thetest stand to advance the moving metal hammer toward the plunger. Whenthe moving metal hammer was within 5 mm of contacting the top of theplunger, the data button on the Dillon module was repeatedly tapped torecord the force at the time of each data button depression, from beforeinitial contact with the syringe plunger until the plunger was stoppedby contact with the front wall of the syringe barrel.

All benchmark and coated syringe barrels were run with five replicates(using a new plunger and barrel for each replicate).

COC syringe barrels made according to the Protocol for Forming COCSyringe barrel were coated with an OMCTS lubricity layer according tothe Protocol for Coating COC Syringe Barrel Interior with OMCTSLubricity layer, assembled and filled with saline, and tested asdescribed above in this Example for lubricity layers. The polypropylenechamber used per the Protocol for Coating COC Syringe Barrel Interiorwith OMCTS Lubricity layer allowed the OMCTS vapor (and oxygen, ifadded—see Table 8) to flow through the syringe barrel and through thesyringe capillary into the polypropylene chamber (although a lubricitylayer is not needed in the capillary section of the syringe in thisinstance). Several different coating conditions were tested, as shown inpreviously mentioned Table 8. All of the depositions were completed onCOC syringe barrels from the same production batch.

The coated samples were then tested using the plunger sliding force testper the protocol of this Example, yielding the results in Table 8, inEnglish and metric force units. The data shows clearly that low powerand no oxygen provided the lowest plunger sliding force for COC andcoated COC syringes. Note that when oxygen was added at lower power (6W) (the lower power being a favorable condition) the plunger slidingforce increased from 1.09 lb., 0.49 Kg (at Power=11 W) to 2.27 lb., 1.03Kg. This indicates that the addition of oxygen may not be desirable toachieve the lowest possible plunger sliding force.

Note also that the best plunger sliding force (Power=11 W, plungersliding force=1.09 lb., 0.49 Kg) was very near the current industrystandard of silicone coated glass (plunger sliding force=0.58 lb., 0.26Kg), while avoiding the problems of a glass syringe such as breakabilityand a more expensive manufacturing process. With additionaloptimization, values equal to or better than the current glass withsilicone performance are expected to be achieved.

The samples were created by coating COC syringe barrels according to theProtocol for Coating COC Syringe Barrel Interior with OMCTS Lubricitylayer. An alternative embodiment of the technology herein, would applythe lubricity layer over another thin film coating, such as SiO_(x), forexample applied according to the Protocol for Coating COC Syringe barrelInterior with SiO_(x).

Example 7

Improved Syringe Barrel Lubricity Layer

The force required to expel a 0.9 percent saline payload from a syringethrough a capillary opening using a plastic plunger was determined forinner wall-coated syringes.

Three types of COC syringe barrels made according to the Protocol forForming COC Syringe barrel were tested: one type having no internalcoating [Uncoated Control], another type with a hexamethyldisiloxane(HMDSO)-based plasma coated internal wall coating [HMDSO Control]according to the Protocol for Coating COC Syringe Barrel Interior withHMDSO Coating, and a third type with an octamethylcyclotetrasiloxane[OMCTS-Inventive Example]-based plasma coated internal wall coatingapplied according to the Protocol for Coating COC Syringe BarrelInterior with OMCTS Lubricity layer. Fresh plastic plungers withelastomeric tips taken from BD Product Becton-Dickinson Product No.306507 were used for all examples. Saline from Product No. 306507 wasalso used.

The plasma coating method and apparatus for coating the syringe barrelinner walls is described in other experimental sections of thisapplication. The specific coating parameters for the HMDSO-based andOMCTS-based coatings are listed in the Protocol for Coating COC SyringeBarrel Interior with HMDSO Coating, the Protocol for Coating COC Syringebarrel Interior with OMCTS Lubricity layer, and Table 9.

The plunger is inserted into the syringe barrel to about 10 millimeters,followed by vertical filling of the experimental syringe through theopen syringe capillary with a separate saline-filled syringe/needlesystem. When the experimental syringe has been filled into the capillaryopening, the syringe is tapped to permit any air bubbles adhering to theinner walls to release and rise through the capillary opening.

The filled experimental syringe barrel/plunger assembly is placedvertically into a home-made hollow metal jig, the syringe assembly beingsupported on the jig at the finger flanges. The jig has a drain tube atthe base and is mounted on Dillon Test Stand with Advanced Force Gauge(Model AFG-50N). The test stand has a metal hammer, moving verticallydownward at a rate of six inches (152 millimeters) per minute. The metalhammer contacts the extended plunger expelling the saline solutionthrough the capillary. Once the plunger has contacted the syringebarrel/capillary interface the experiment is stopped.

During downward movement of the metal hammer/extended plunger,resistance force imparted on the hammer as measured on the Force Gaugeis recorded on an electronic spreadsheet. From the spreadsheet data, themaximum force for each experiment is identified.

Table 9 lists for each Example the Maximum Force average from replicatecoated COC syringe barrels and the Normalized Maximum Force asdetermined by division of the coated syringe barrel Maximum Forceaverage by the uncoated Maximum Force average.

The data indicates all OMCTS-based inner wall plasma coated COC syringebarrels (Inventive Examples C, E, F, G, H) demonstrate much lowerplunger sliding force than uncoated COC syringe barrels (uncoatedControl Examples A & D) and surprisingly, also much lower plungersliding force than HMDSO-based inner wall plasma coated COC syringebarrels (HMDSO control Example B). More surprising, an OMCTS-basedcoating over a silicon oxide (SiO_(x)) gas barrier layer maintainsexcellent low plunger sliding force (Inventive Example F). The bestplunger sliding force was Example C (Power=8, plunger sliding force=1.1lb., 0.5 Kg). It was very near the current industry standard of siliconecoated glass (plunger sliding force=0.58 lb., 0.26 Kg.), while avoidingthe problems of a glass syringe such as breakability and a moreexpensive manufacturing process. With additional optimization, valuesequal to or better than the current glass with silicone performance areexpected to be achieved.

Example 8

Fabrication of COC Syringe Barrel with Exterior Coating

Prophetic Example

A COC syringe barrel formed according to the Protocol for Forming COCSyringe barrel is sealed at both ends with disposable closures. Thecapped COC syringe barrel is passed through a bath of Daran® 8100 SaranLatex (Owensboro Specialty Plastics). This latex contains five percentisopropyl alcohol to reduce the surface tension of the composition to 32dynes/cm). The latex composition completely wets the exterior of the COCsyringe barrel. After draining for 30 seconds, the coated COC syringebarrel is exposed to a heating schedule comprising 275 .degree. F. (135.degree. C.) for 25 seconds (latex coalescence) and 122 .degree. F. (50.degree. C.) for four hours (finish cure) in respective forced airovens. The resulting PVdC film is 1/10 mil (2.5 microns) thick. The COCsyringe barrel and PVdC-COC laminate COC syringe barrel are measured forOTR and WVTR using a MOCON brand Oxtran 2/21 Oxygen PermeabilityInstrument and Permatran-W 3/31 Water Vapor Permeability Instrument,respectively.

Predicted OTR and WVTR values are listed in Table 10, which shows theexpected Barrier Improvement Factor (BIF) for the laminate would be 4.3(OTR-BIF) and 3.0 (WVTR-BIF), respectively.

Example 9

Atomic Compositions of PECVD Applied OMCTS and HMDSO Coatings

COC syringe barrel samples made according to the Protocol for FormingCOC Syringe barrel, coated with OMCTS (according to the Protocol forCoating COC Syringe Barrel Interior with OMCTS Lubricity layer) orcoated with HMDSO according to the Protocol for Coating COC SyringeBarrel Interior with HMDSO Coating were provided. The atomiccompositions of the coatings derived from OMCTS or HMDSO werecharacterized using X-Ray Photoelectron Spectroscopy (XPS).

XPS data is quantified using relative sensitivity factors and a modelthat assumes a homogeneous layer. The analysis volume is the product ofthe analysis area (spot size or aperture size) and the depth ofinformation. Photoelectrons are generated within the X-ray penetrationdepth (typically many microns), but only the photoelectrons within thetop three photoelectron escape depths are detected. Escape depths are onthe order of 15-35 .ANG., which leads to an analysis depth of −50-100.ANG. Typically, 95% of the signal originates from within this depth.

The following analytical parameters were used:

-   -   Instrument: PHI Quantum 2000    -   X-ray source: Monochromated Alk_1486.6 eV    -   Acceptance Angle: +23°    -   Take-off angle: 45°    -   Analysis area: 600 μm    -   Change Correction: C1s 284.8 eV    -   Ion Gun Conditions: Ar+, 1 keV, 2×2 mm raster    -   Sputter Rate: 15.6 Å/min (SiO2 Equivalent)

Table 11 provides the atomic concentrations of the elements detected.XPS does not detect hydrogen or helium. Values given are normalized to100 percent using the elements detected. Detection limits areapproximately 0.05 to 1.0 atomic percent.

From the coating composition results and calculated starting monomerprecursor elemental percent in Table 11, while the carbon atom percentof the HMDSO-based coating is decreased relative to starting HMDSOmonomer carbon atom percent (54.1% down to 44.4%), surprisingly theOMCTS-based coating carbon atom percent is increased relative to theOMCTS monomer carbon atom percent (34.8% up to 48.4%), an increase of 39atomic %, calculated as follows:100%[(48.4/34.8)−1]=39 at. %.

Also, while the silicon atom percent of the HMDSO-based coating isalmost unchanged relative to starting HMDSO monomer silicon atom percent(21.8% to 22.2%), surprisingly the OMCTS-based coating silicon atompercent is significantly decreased relative to the OMCTS monomer siliconatom percent (42.0% down to 23.6%), a decrease of 44 atomic %. With boththe carbon and silicon changes, the OMCTS monomer to coating behaviordoes not trend with that observed in common precursor monomers (e.g.HMDSO). See, e.g., Hans J. Griesser, Ronald C. Chatelier, Chris Martin,Zoran R. Vasic, Thomas R. Gengenbach, George Jessup J. Biomed. Mater.Res. (Appl. Biomater.) 53: 235-243, 2000.

Example 10

Volatile Components from Plasma Coatings (“Outgassing”)

COC syringe barrel samples made according to the Protocol for FormingCOC Syringe barrel, coated with OMCTS (according to the Protocol forCoating COC Syringe Barrel Interior with OMCTS Lubricity layer) or withHMDSO (according to the Protocol for Coating COC Syringe Barrel Interiorwith HMDSO Coating) were provided. Outgassing gas chromatography/massspectroscopy (GC/MS) analysis was used to measure the volatilecomponents released from the OMCTS or HMDSO coatings.

The syringe barrel samples (four COC syringe barrels cut in halflengthwise) were placed in one of the 1½″ (37 mm) diameter chambers of adynamic headspace sampling system (CDS 8400 auto-sampler). Prior tosample analysis, a system blank was analyzed. The sample was analyzed onan Agilent 7890A Gas Chromatograph/Agilent 5975 Mass Spectrometer, usingthe following parameters, producing the data set out in Table 12:

GC Column: 30 m.times.0.25 mm DB-5MS (J&W Scientific), 0.25 .mu.m filmthickness [0872] Flow rate: 1.0 ml/min, constant flow mode [0873]Detector: Mass Selective Detector (MSD) [0874] Injection Mode: Splitinjection (10:1 split ratio) [0875] Outgassing Conditions: 1½″ (37 mm)Chamber, purge for three hour at 85 .degree. C., flow 60 ml/min [0876]Oven temperature: 40 .degree. C. (5 min.) to 300 .degree. C. @10.degree. C./min.; hold for 5 min. at 300 .degree. C.

-   -   GC Column 30 m×0.25 mm DB-5MS (J&W Scientific), 0.25 μm film        thickness    -   Flow rate: 1.0 ml/min, constant flow mode    -   Detector: Mass Selective Detector (MSD)    -   Injection mode: Split injection (10:1 split ratio)    -   Outgassing Conditions: 1½″ (37 mm) Chamber, purge for three hour        at 85° C., Flow 60 ml/mn    -   Oven temperature 40° C. (5 min.) to 300° C. at 10° C./min.; hold        for 5 min. at 300° C.

The outgassing results from Table 12 clearly indicated a compositionaldifferentiation between the HMDSO-based and OMCTS-based lubricity layerstested. HMDSO-based compositions outgassed trimethylsilanol [(Me)₃SiOH]but outgassed no measured higher oligomers containing repeating-(Me)₂SiO— moieties, while OMCTS-based compositions outgassed nomeasured trimethylsilanol [(Me)₃SiOH] but outgassed higher oligomerscontaining repeating -(Me)₂SiO— moieties. It is contemplated that thistest can be useful for differentiating HMDSO-based coatings fromOMCTS-based coatings.

Without limiting the invention according to the scope or accuracy of thefollowing theory, it is contemplated that this result can be explainedby considering the cyclic structure of OMCTS, with only two methylgroups bonded to each silicon atom, versus the acyclic structure ofHMDSO, in which each silicon atom is bonded to three methyl groups.OMCTS is contemplated to react by ring opening to form a diradicalhaving repeating -(Me)₂SiO— moieties which are already oligomers, andcan condense to form higher oligomers. HMDSO, on the other hand, iscontemplated to react by cleaving at one O—Si bond, leaving one fragmentcontaining a single O—Si bond that recondenses as (Me)₃SiOH and theother fragment containing no O—Si bond that recondenses as [(Me)₃Si]₂.

The cyclic nature of OMCTS is believed to result in ring opening andcondensation of these ring-opened moieties with outgassing of higher MWoligomers (26 ng/test). In contrast, HMDSO-based coatings are believednot to provide any higher oligomers, based on the relativelylow-molecular-weight fragments from HMDSO.

Example 11

Density Determination of Plasma Coatings Using X-Ray Reflectivity (XRR)

Sapphire witness samples (0.5.times.0.5.times.0.1 cm) were glued to theinner walls of separate PET tubes, made according to the Protocol forForming PET tubes. The sapphire witness-containing PET tubes were coatedwith OMCTS or HMDSO (both according to the Protocol for Coating COCSyringe Barrel Interior with OMCTS Lubricity layer, deviating all with2.times. power). The coated sapphire samples were then removed and X-rayreflectivity (XRR) data were acquired on a PANalytical X'Pertdiffractometer equipped with a parabolic multilayer incident beammonochromator and a parallel plate diffracted beam collimator. A twolayer Si_(w)O_(x)C_(y)H_(z) model was used to determine coating densityfrom the critical angle measurement results. This model is contemplatedto offer the best approach to isolate the true Si_(w)O_(x)C_(y)H_(z)coating. The results are shown in Table 13.

From Table 11 showing the results of Example 9, the lower oxygen (28%)and higher carbon (48.4%) composition of OMCTS versus HMDSO wouldsuggest OMCTS should have a lower density, due to both atomic massconsiderations and valency (oxygen=2; carbon=4). Surprisingly, the XRRdensity results indicate the opposite would be observed, that is, theOMCTS density is higher than HMDSO density.

Without limiting the invention according to the scope or accuracy of thefollowing theory, it is contemplated that there is a fundamentaldifference in reaction mechanism in the formation of the respectiveHMDSO-based and OMCTS-based coatings. HMDSO fragments can more easilynucleate or react to form dense nanoparticles which then deposit on thesurface and react further on the surface, whereas OMCTS is much lesslikely to form dense gas phase nanoparticles. OMCTS reactive species aremuch more likely to condense on the surface in a form much more similarto the original OMCTS monomer, resulting in an overall less densecoating.

Example 12

Thickness Uniformity of PECVD Applied Coatings

Samples were provided of COC syringe barrels made according to theProtocol for Forming COC Syringe barrel and respectively coated withSiO_(x) according to the Protocol for Coating COC Syringe BarrelInterior with SiO_(x) or an OMCTS-based lubricity layer according to theProtocol for Coating COC Syringe Barrel Interior with OMCTS Lubricitylayer. Samples were also provided of PET tubes made according to theProtocol for Forming PET Tube, respectively coated and uncoated withSiOx according to the Protocol for Coating Tube Interior with SiO_(x)and subjected to an accelerated aging test. Transmission electronmicroscopy (TEM) was used to measure the thickness of the PECVD-appliedcoatings on the samples. The previously stated TEM procedure of Example4 was used. The method and apparatus described by the SiO_(x) andlubricity layer protocols used in this example demonstrated uniformcoating as shown in Table 14.

Example 13

Lubricity Layers

COC syringe barrels made according to the Protocol for Forming COCSyringe Barrel were coated with a lubricity layer according to theProtocol for Coating COC Syringe Barrel Interior with OMCTS Lubricitylayer. The results are provided in Table 15. The results show that thetrend of increasing the power level, in the absence of oxygen, from 8 to14 Watts was to improve the lubricity of the coating. Furtherexperiments with power and flow rates can provide further enhancement oflubricity.

Example 14

Lubricity Layers

Hypothetical Example

Injection molded cyclic olefin copolymer (COC) plastic syringe barrelsare made according to the Protocol for Forming COC Syringe Barrel. Someare uncoated (“control”) and others are PECVD lubricity coated accordingto the Protocol for Coating COC Syringe Barrel Interior with OMCTSLubricity layer (“lubricated syringe”). The lubricated syringes andcontrols are tested to measure the force to initiate movement of theplunger in the barrel (breakout force) and the force to maintainmovement of the plunger in the barrel (plunger sliding force) using aGenesis Packaging Automated Syringe Force Tester, Model AST.

The test is a modified version of the ISO 7886-1:1993 test. Thefollowing procedure is used for each test. A fresh plastic plunger withelastomeric tip taken from Becton Dickinson Product No. 306507 (obtainedas saline prefilled syringes) is removed from the syringe assembly. Theelastomeric tip is dried with clean dry compressed air. The elastomerictip and plastic plunger are then inserted into the COC plastic syringebarrel to be tested with the plunger positioned even with the bottom ofthe syringe barrel. The filled syringes are then conditioned asnecessary to achieve the state to be tested. For example, if the testobject is to find out the effect of lubricant coating on the breakoutforce of syringes after storing the syringes for three months, thesyringes are stored for three months to achieve the desired state.

The syringe is installed into a Genesis Packaging Automated SyringeForce Tester. The tester is calibrated at the start of the test per themanufacturer's specification. The tester input variables are Speed=100mm/minute, Range=10,000. The start button is pushed on the tester. Atcompletion of the test, the breakout force (to initiate movement of theplunger in the barrel) and the plunger sliding force (to maintainmovement) are measured, and are found to be substantially lower for thelubricated syringes than for the control syringes.

FIG. 14 shows a vessel processing system 20 according to an exemplaryembodiment of the present invention. The vessel processing system 20comprises, inter alia, a first processing station 5501 and a secondprocessing station 5502. Examples for such processing stations are forexample depicted in FIG. 1, reference numerals 24, 26, 28, 30, 32 and34.

The first vessel processing system 5501 contains a vessel holder 38which holds a seated vessel 80. Although FIG. 14 depicts a blood tube80, the vessel can also be, for example, a syringe body, a vial, acuvette, a catheter or a pipette. The vessel can, for example, be madeof glass or plastic. In case of plastic vessels, the first processingstation can also comprise a mold for molding the plastic vessel.

After the first processing at the first processing station (whichprocessing can comprise molding of the vessel, a first inspection of thevessel for defects, coating of the interior surface of the vessel and asecond inspection of the vessel for defects, for example of the interiorcoating), the vessel holder 38 is transported together with the vessel80 to a second vessel processing station 5502. This transportation isperformed by a conveyor arrangement 70, 72, 74. For example, a gripperor several grippers can be provided for gripping the vessel holder 38and/or the vessel 80 in order to move the vessel/holder combination tothe next processing station 5502. Alternatively, only the vessel can bemoved without the holder. However, it can be advantageous to move theholder together with the vessel in which case the holder is adapted suchthat it can be transported by the conveyor arrangement.

While the invention has been illustrated and described in detail in thedrawings and foregoing description, such illustration and descriptionare to be considered illustrative or exemplary and not restrictive; theinvention is not limited to the disclosed embodiments. Other variationsto the disclosed embodiments can be understood and effected by thoseskilled in the art and practicing the claimed invention, from a study ofthe drawings, the disclosure, and the appended claims. In the claims,the word “comprising” does not exclude other elements or steps, and theindefinite article “a” or “an” does not exclude a plurality. The merefact that certain measures are recited in mutually different dependentclaims does not indicate that a combination of these measures cannot beused to advantage. Any reference signs in the claims should not beconstrued as limiting the scope.

TABLE 1 COATED COC TUBE OTR AND WVTR MEASUREMENT OTR WVTR O—Si O₂ (cc/(mg/ Coating Power Flow Flow Time Tube. Tube. ID (Watts) O—Si (sccm)(sccm) (sec) Day) Day) No 0.215 0.27 Coating A 50 HMDSO 6 90 14 0.0230.07 B 50 HMDSO 6 90 14 0.024 0.10 C 50 HMDSO 6 90  7 0.026 0.10

TABLE 2 COATED PET TUBE OTR AND WVTR MEASUREMENT OTR WVTR O—Si O₂ (cc/(mg/ Coating Power Flow Flow Time Tube. Tube. BIF BIF ID (Watts) O—Si(sccm) (sccm) (sec) Day) Day) (OTR) (WVTR) Uncoated 0.0078 3.65 — —Control SiO_(x) 50 HMDSO 6 90 3 0.0035 1.95 2.2 1.9

TABLE 3 COATED PET TUBE OTR WITH MECHANICAL SCRATCH DEFECTS MechanicalO—Si O₂ Treat Scratch OTR Power Flow Flow Time Length (cc/tube. ExampleO—Si (Watts) (sccm) (sccm) (sec) (mm) day)* OTR BIF Uncoated 0.0052Control Inventive HMDSO 50 6 90 3 0 0.0014 3.7 Inventive HMDSO 50 6 90 31 0.0039 1.3 Inventive HMDSO 50 6 90 3 2 0.0041 1.3 Inventive HMDSO 50 690 3 10  0.0040 1.3 Inventive HMDSO 50 6 90 3 20  0.0037 1.4 *average oftwo tubes

TABLE 4 COATED COC SYRINGE BARREL OTR AND WVTR MEASUREMENT O—Si O₂ OTRWVTR Flow Flow Coating (cc/ (mg/ Syringe O—Si Power Rate Rate TimeBarrel. Barrel. BIF BIF Example Coating Composition (Watts) (sccm)(sccm) (sec) Day) Day) (OTR) (WVTR) A Uncoated 0.032 0.12 Control BSiO_(x) HMDSO 44 6 90 7 0.025 0.11 1.3 1.1 Inventive Example C SiO_(x)HMDSO 44 6 105 7 0.021 0.11 1.5 1.1 Inventive Example D SiO_(x) HMDSO 506 90 7 0.026 0.10 1.2 1.2 Inventive Example E SiO_(x) HMDSO 50 6 90 14 0.024 0.07 1.3 1.7 Inventive Example F SiO_(x) HMDSO 52 6 97.5 7 0.0220.12 1.5 1.0 Inventive Example G SiO_(x) HMDSO 61 6 105 7 0.022 0.11 1.41.1 Inventive Example H SiO_(x) HMDSO 61 6 120 7 0.024 0.10 1.3 1.2Inventive Example I SiO_(x) HMDZ 44 6 90 7 0.022 0.10 1.5 1.3 InventiveExample J SiO_(x) HMDZ 61 6 90 7 0.022 0.10 1.5 1.2 Inventive Example KSiO_(x) HMDZ 61 6 105 7 0.019 0.10 1.7 1.2 Inventive Example

TABLE 5 SIO_(x) COATING THICKNESS (NANOMETERS) DETECTED BY TEM OxygenHMDSO Flow Thickness Power Flow Rate Rate Sample O-Si (nm) (Watts)(sccm) (sccm) Inventive HMDSO 25-50 39 6 60 Example A Inventive HMDSO20-35 39 6 90 Example B

TABLE 6 ATOMIC RATIOS OF THE ELEMENTS DETECTED (in parentheses,Concentrations in percent, normalized to 100% of elements detected)Plasma Sample Coating Si O C PET Tube - — 0.08 (4.6%) 1 (31.5%) 2.7(63.9%) Comparative Example Polyethylene — 1 (28.6%) 2.5 (71.4%)Terephthalate- Calculated Coated PET SiO_(x) 1 (39.1%) 2.4 (51.7%) 0.57(9.2%) Tube - Inventive Example

TABLE 7 EXTENT OF HOLLOW CATHODE PLASMA IGNITION Hollow Cathode StainingSample Power Time Plasma Ignition Result A 25 Watts 7 sec No Ignition ingas inlet 310, good Ignition in restricted area 292 B 25 Watts 7 secIgnition in gas inlet 310 and poor restricted area 292 C  8 Watts 9 secNo Ignition in gas inlet 310, better Ignition in restricted area 292 D30 Watts 5 sec No Ignition in gas inlet 310 or best restricted area 292

TABLE 8 SYRINGE BARRELS WITH LUBRICITY LAYER, ENGLISH UNITS O—Si O₂ Avg.Power, Flow, Flow, time Force, St. Sample (Watts) (sccm) (sccm) (sec)(lb.) dev. Glass with No No No No 0.58 0.03 Silicone coating coatingcoating coating Uncoated No No No No 3.04 0.71 COC coating coatingcoating coating A 11 6 0 7 1.09 0.27 B 17 6 0 14 2.86 0.59 C 33 6 0 143.87 0.34 D  6 6 90  30 2.27 0.49 Uncoated COC — — — — 3.9 0.6 SiO_(x)on COC 4.0 1.2 E 11 1.25 0 5 2.0 0.5 F 11 2.5 0 5 2.1 0.7 G 11 5 0 5 2.60.6 H 11 2.5 0 10 1.4 0.1 I 22 5 0 5 3.1 0.7 J 22 2.5 0 10 3.3 1.4 K 225 0 5 3.1 0.4 SYRINGE BARRELS WITH LUBRICITY LAYER, METRIC UNITS O—Si O₂Avg. Power, Flow, Flow, time Force, St. Sample (Watts) (sccm) (sccm)(sec) (Kg.) dev. Glass syringe No No No No 0.26 0.01 with sprayedcoating coating coating coating silicone Uncoated COC No No No No 1.380.32 coating coating coating coating A 11 6 0 7 0.49 0.12 B 17 6 0 141.29 0.27 C 33 6 0 14 1.75 0.15 D  6 6 90  30 1.03 0.22 Uncoated COC — —— 1.77 0.27 SiO_(x) on COC, 1.81 0.54 per protocol E 11 1.25 — 5 0.910.23 F 11 2.5 — 5 0.95 0.32 G 11 5 — 5 1.18 0.27 H 11 2.5 — 10 0.63 0.05I 22 5 — 5 1.40 0.32 J 22 2.5 — 10 1.49 0.63 K 22 5 — 5 1.40 0.18

TABLE 9 PLUNGER SLIDING FORCE MEASUREMENTS OF HMDSO- AND OMCTS-BASEDPLASMA COATINGS Coating Coating Si—O Coating Maximum Normalized TimeFlow Rate Power Force Maximum Example Description Monomer (sec) (sccm)(Watts) (lb, kg.) Force A uncoated 3.3, 1.5 1.0 Control B HMDSO HMDSO 76 8 4.1, 1.9 1.2 Coating C OMCTS OMCTS 7 6 8 1.1, 0.5 0.3 Lubricitylayer D uncoated 3.9, 1.8 1.0 Control E OMCTS OMCTS 7 6 11 2.0, 0.9 0.5Lubricity layer F Two Layer 1 COC 14 6 50 2.5, 1.1 0.6 Coating SyringeBarrel + SiO_(x) 2 OMCTS 7 6 8 Lubricity layer G OMCTS OMCTS 5 1.25 11  2, 0.9 0.5 Lubricity layer H OMCTS OMCTS 10 1.25 11 1.4, 0.6 0.4Lubricity layer

TABLE 10 OTR AND WVTR MEASUREMENTS (Prophetic) OTR WVTR Sample(cc/barrel · day) (gram/barrel · day) COC syringe- 4.3 X 3.0 YComparative Example PVdC-COC laminate X Y COC syringe-Inventive Example

TABLE 11 ATOMIC CONCENTRATIONS (IN PERCENT, NORMALIZED TO 100% OFELEMENTS DETECTED) AND TEM THICKNESS Plasma Sample Coating Si O CHMDSO-based Si_(w)O_(x)C_(y) 0.76 (22.2%) 1 (33.4%) 3.7 (44.4%) CoatedCOC syringe barrel OMCTS-based Si_(w)O_(x)C_(y) 0.46 (23.6%) 1 (28%) 4.0(48.4%) Coated COC syringe barrel HMDSO Monomer- Si₂OC₆ 2 (21.8%) 1(24.1%) 6 (54.1%) calculated OMCTS Monomer- Si₄O₄C₈ 1 (42%) 1 (23.2%) 2(34.8%) calculated

TABLE 12 VOLATILE COMPONENTS FROM SYRINGE OUTGASSING Coating Me₃SiOHHigher SiOMe Monomer (ng/test) oligomers (ng/test) Uncoated COC syringe-Uncoated ND ND Comparative Example HMDSO-based Coated HMDSO 58 ND COCsyringe- Comparative Example OMCTS-based Coated OMCTS ND 26 COCsyringe-Inventive Example

TABLE 13 PLASMA COATING DENSITY FROM XRR DETERMINATION Density SampleLayer g/cm³ HMDSO-based Coated Sapphire- Si_(w)O_(x)C_(y)H_(z) 1.21Comparative Example OMCTS-based Coated Sapphire- Si_(w)O_(x)C_(y)H_(z)1.46 Inventive Example

TABLE 14 THICKNESS OF PECVD COATINGS BY TEM TEM TEM TEM Thickness SampleID Thickness I Thickness II III Protocol for Forming 164 nm 154 nm 167nm COC Syringe Barrel; Protocol for Coating COC Syringe Barrel Interiorwith SiO_(x) Protocol for Forming  55 nm  48nm  52 nm COC SyringeBarrel; Protocol for Coating COC Syringe Barrel Interior with OMCTSLubricity layer Protocol for  28 nm  26 nm  30 nm Forming PET Tube;Protocol for Coating Tube Interior with SiO_(x) Protocol for — — —Forming PET Tube (uncoated)

TABLE 15 OMCTS LUBRICITY LAYER PERFORMANCE (English Units) PercentAverage Force Plunger Reduction OMCTS Force (vs Power Flow Sample(lbs.)* uncoated) (Watts) (sccm) Comparative 3.99 — — — (no coating)Sample A 1.46 63% 14 0.75 Sample B 1.79 55% 11 1.25 Sample C 2.09 48% 81.75 Sample D 2.13 47% 14 1.75 Sample E 2.13 47% 11 1.25 Sample F 2.9925% 8 0.75 *Average of 4 replicates

TABLE 15 OMCTS LUBRICITY LAYER PERFORMANCE (Metric Units) PercentAverage Force Plunger Reduction OMCTS Force (vs Power Flow Sample(lbs.)* uncoated) (Watts) (sccm) Comparative 1.81 — — — (no coating)Sample A 0.66 63% 14 0.75 Sample B 0.81 55% 11 1.25 Sample C 0.95 48% 81.75 Sample D 0.96 47% 14 1.75 Sample E 0.96 47% 11 1.25 Sample F 1.3525% 8 0.75

Above force measurements are the average of 4 samples.

The invention claimed is:
 1. A syringe comprising: a barrel and a plunger, the barrel having an inner surface defining a lumen and the plunger having a side surface engaging the barrel inner surface, wherein the inner surface is a substrate comprising a polymer, coated with a barrier coating of SiO_(x), in which x is from about 1.5 to about 2.9, and a lubricity layer applied to the barrier coating of SiO_(x) and configured to provide a lower plunger sliding force or breakout force than the uncoated substrate, the lubricity layer having the following atomic ratios, measured by X-ray photoelectron spectroscopy (XPS), Si_(w)O_(x)C_(y), where w is 1, x in this formula is from about 0.5 to 2.4, and y is from about 0.6 to about 3; the lubricity layer having a thickness by transmission electron microscopy (TEM) between 10 and 1000 nm; the lubricity layer deposited by plasma enhanced chemical vapor deposition (PECVD) under conditions effective to form a coating from a precursor comprising a linear siloxane, a monocyclic siloxane, or a combination of any two or more of these precursors.
 2. The syringe of claim 1, in which the precursor comprises octamethylcyclotetrasiloxane (OMCTS).
 3. The syringe of claim 1, in which the polymer comprises an olefin polymer.
 4. The syringe of claim 1, in which the lubricity layer is configured to provide a lower plunger sliding force than the uncoated substrate.
 5. The syringe of claim 1, in which the lubricity layer reduces the syringe plunger sliding force moving through the syringe barrel at least 45 percent relative to the uncoated syringe barrel.
 6. The syringe of claim 5, in which the plunger sliding force is measured in a Genesis Packaging Automated Syringe Force Tester at a speed of 100 mm/minute, Range=10,000.
 7. The syringe of claim 1, in which the lubricity layer reduces the syringe plunger sliding force moving through the syringe barrel at least 60 percent relative to the uncoated syringe barrel.
 8. The syringe of claim 1, in which the lubricity layer is configured to provide a lower plunger breakout force than the uncoated substrate.
 9. The syringe of claim 1, in which the lubricity layer reduces the syringe plunger breakout force at least 45 percent relative to the uncoated syringe barrel.
 10. The syringe of claim 9, in which the syringe plunger breakout force is measured in a Genesis Packaging Automated Syringe Force Tester at a speed of 100 mm/minute, Range=10,000.
 11. The syringe of claim 1, in which the lubricity layer reduces the syringe plunger breakout force at least 60 percent relative to the uncoated syringe barrel.
 12. The syringe of claim 1, in which the lubricity layer has a density between 1.25 and 1.65 g/cm³ as determined by X-ray reflectivity (XRR).
 13. The syringe of claim 1, in which the lubricity layer has an outgas component as determined by gas chromatography/mass spectrometry substantially free of trimethylsilanol.
 14. The syringe of claim 1, in which the lubricity layer has an outgas component as determined by gas chromatography/mass spectrometry having at least 10 ng/test of oligomers containing repeating -(Me)2SiO— moieties, as determined by gas chromatography/mass spectrometry using the following test conditions: GC Column: 30 m×0.25 mm DB-5MS (J&W Scientific), 0.25 μm film thickness Flow rate: 1.0 ml/min, constant flow mode Detector: Mass Selective Detector (MSD) Injection Mode: Split injection (10:1 split ratio) Outgassing Conditions: 1 W (37 mm) Chamber, purge for three hour at 85° C., flow 60 ml/min Oven temperature: 40° C. (5 min.) to 300° C. @10° C./min.; hold for 5 min, at 300° C.
 15. The syringe of claim 1, in which the lubricity layer has atomic concentrations from 25 to 45% carbon, 25 to 65% silicon, and 10 to 35% oxygen.
 16. The syringe of claim 1, in which the lumen has a void volume of from 0.5 to 50 mL.
 17. The syringe of claim 1, in which the lubricity layer has a lower wetting tension than the uncoated surface.
 18. The syringe of claim 1, in which the lubricity layer has a thickness by transmission electron microscopy (TEM) between 10 and 500 nm.
 19. The syringe of claim 1, in which the lubricity layer has atomic concentrations normalized to 100% carbon, oxygen, and silicon, as determined by X-ray photoelectron spectroscopy (XPS), of less than 50% carbon and more than 25% silicon.
 20. The syringe of claim 1, in which at least one intervening layer of another material separates the barrier coating and lubricity layer.
 21. The syringe of claim 1, in which the lubricity layer is between 100 nm and 500 nm thick.
 22. The syringe of claim 1, in which the maximum plunger sliding force of the syringe is between 1.1 lb. (4.9 N) and 2.5 lb. (11.1 N).
 23. The syringe of claim 1, in which the maximum plunger sliding force of the syringe is between 1.1 lb. (4.9 N) and 2 lb. (8.9 N).
 24. The syringe of claim 1, in which the maximum plunger sliding force of the syringe is between 1.1 lb. (4.9 N) and 1.4 lb. (6.2 N). 